49ers vs Colts Prediction, Picks & Odds | 22 Dec 2025

NFL Betting Preview: Niners vs Colts

The San Francisco 49ers face the Indianapolis Colts in this Week 16 Monday Night Football clash at Lucas Oil Stadium, with kickoff scheduled for 20:15 on Monday, December 22.

With the Colts capable of remaining close to the Niners, backing the Shoe on the spread could be the way forward. Odds of -105 is available that the +5.5 is covered.

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San Francisco 49ers claimed a home victory in their previous game. A 37-24 triumph against Tennessee Titans at Levi's Stadium made it four straight wins. The 49ers put up 430 yards, including 292 passing and 138 rushing yards. The offense generated 28 first downs and produced 4 touchdowns.

Indianapolis Colts have been beaten in their last four games. On the road at Lumen Field, Seattle Seahawks recently beat them 18-16. The Colts moved the ball for 215 yards, breaking down to 118 passing and 97 rushing yards. They managed 14 first downs to go along with a single touchdown.

Head-to-Head Statistics

These two teams last met at Levi's Stadium, with the Colts claiming the win. Beating the Niners by a 30-18 scoreline.

Quarterbacks

Brock Purdy

248.5 Passing Yards

Over -112

Under -112

Philip Rivers

160.5 Passing Yards

Over -112

Under -112

49ers vs Colts Prediction & Picks

Be fully equipped for 49ers vs Colts with our betting guide, offering a key match prediction, a correct score recommendation, top player prop picks and a bet builder tailored for value.

Game Prediction

We’re really sweet on the Colts putting up a fight in this NFL showdown and that compels us to bet the underdogs against the spread. You can get -105 when it comes to the +5.5 that is available.

The NFL handicappers at Sportsgambler.com stay on top of the latest injuries, while recent form also shapes our picks. We combine this insight with up-to-date stats for sharper predictions.

Key 49ers vs Colts stats:

• The +5.5 line has been covered by Colts in 9 consecutive games at home.
• The +5.5 line has been covered by Colts in 17 of their last 20 games at home.
• The +5.5 line has been covered by Colts in 11 of their last 14 games this season.
• The -5.5 line hasn’t been covered by 49ers in 7 of their last 10 games on the road.
• The -5.5 line hasn’t been covered by 49ers in 13 of their last 20 games.

Colts +5.5 Probability

If you go by the best betting sites, our pick has a 51.3% chance of winning. In the opinion of our cappers, there’s actually a probability of success closer to 60%. This bet can therefore be backed with confidence.

A Bet Builder provides you with the chance to combine the Colts against the spread with other picks. For every additional selection, the odds are boosted.

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Our Game Prediction

Colts +5.5 @ -105 Bet Now

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Disclosure: This preview contains affiliate links; we may earn a commission at no extra cost to you. T&Cs apply. We only recommend licensed and regulated operators. See our Editorial Policy. Pick odds and lines reflect the price available at the time of publication (02:25, 21 December 2025). Live market odds are updated regularly and may differ. 18+ (or legal age) | Gamble Responsibly.

Player Prop Picks

Top Pick: George Kittle Anytime TD +120

You can back George Kittle (Niners) at +120 to break the plane of the end zone. We believe this is the best of the player props, with attractive odds available when it comes to betting him to score a touchdown at any time.

Latest George Kittle Player Prop Odds

Touchdown

Anytime

+115

First

+700

Receiving Yards

Over 66.5

-112

Under 66.5

-112

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Philip Rivers Under 157.5 Passing Yards -114

You can place a bet on Philip Rivers (Colts) at -114 to record fewer than 157.5 passing yards. He may fall short of the QB Passing Yards line, making this prop bet a strong pick.

Latest Philip Rivers Player Prop Odds

Touchdown

Anytime

+3300

First

+10000

Passing Yards

Over 160.5

-112

Under 160.5

-112

Rushing Yards

Over 0.5

+220

Under 0.5

-303

Pick odds and lines correct at publication. Live market odds are updated regularly and may differ. T&Cs apply. 18+ (or legal age) | Gamble Responsibly.

Correct Score Prediction

49ers 28 - 27 Colts

The 49ers are available at huge odds to secure a 28-27 win and they might have the edge. This should be a close battle and there won’t be much between the teams.

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49ers vs Colts Odds

The odds and lines below are updated regularly and may differ from the prices shown in our picks, which are captured at the time of publication.

The San Francisco 49ers odds have been priced up by the sportsbooks and they are -154 betting favorites to land victory in this game which means a 61% chance of winning. Indianapolis Colts are trading at bigger odds than their opponents and they can be backed at +130.

The spread is calculated to be 3, while total points comes in at 46.5. There are many ways to bet on the NFL including the Totals. Those who wager Under 46.5 can get -110.

Whether you are wagering pre-game or in-game on the National Football League, the best betting apps offer a wide range of game lines and team props. The selections are practically endless and it’s great to have so many different options.

Moneyline

49ers

-154

Colts

+130

Point Spread

49ers -3

-115

Colts +3

-105

Total Points

Under 46.5

-110

Over 46.5

-110

Those interested in favorite Jonathan Taylor to score the first touchdown are able to get +300. If the Anytime TD angle makes appeal, then this is -250.

Touchdown

Jonathan Taylor (Colts)

First TD

+300

Anytime TD

-250

Christian McCaffrey (49ers)

First TD

+400

Anytime TD

-179

George Kittle (49ers)

First TD

+700

Anytime TD

+115

Jauan Jennings (49ers)

First TD

+850

Anytime TD

+135

Ricky Pearsall (49ers)

First TD

+900

Anytime TD

+155

Tyler Warren (Colts)

First TD

+1200

Anytime TD

+220

Michael Pittman Jr. (Colts)

First TD

+1700

Anytime TD

+330

Josh Downs (Colts)

First TD

+1700

Anytime TD

+340

Alec Pierce (Colts)

First TD

+2200

Anytime TD

+490

Kendrick Bourne (49ers)

First TD

+2200

Anytime TD

+450

Brian Robinson Jr. (49ers)

First TD

+2200

Anytime TD

+380

Demarcus Robinson (49ers)

First TD

+2700

Anytime TD

+550

Ameer Abdullah (Colts)

First TD

+2700

Anytime TD

+600

Brock Purdy (49ers)

First TD

+3000

Anytime TD

+600

Kyle Juszczyk (49ers)

First TD

+4000

Anytime TD

+900

Mo Alie-Cox (Colts)

First TD

+8000

Anytime TD

+1500

Tyler Goodson (Colts)

First TD

+8000

Anytime TD

+1800

DJ Giddens (Colts)

First TD

+8000

Anytime TD

+1800

James Jordan (49ers)

First TD

+10000

Anytime TD

+2700

Drew Ogletree (Colts)

First TD

+10000

Anytime TD

+2200

Isaac Guerendo (49ers)

First TD

+10000

Anytime TD

+2700

Will Mallory (Colts)

First TD

+10000

Anytime TD

+2200

Philip Rivers (Colts)

First TD

+10000

Anytime TD

+3300

Laquon Treadwell (Colts)

First TD

+10000

Anytime TD

+2700

Jake Tonges (49ers)

First TD

+10000

Anytime TD

+1600

Jordan Watkins (49ers)

First TD

+10000

Anytime TD

+1100

Skyy Moore (49ers)

First TD

+10000

Anytime TD

+1100

Luke Farrell (49ers)

First TD

+10000

Anytime TD

+950

Anthony Gould (Colts)

First TD

+10000

Anytime TD

+1900

Receiving Yards

George Kittle (49ers)

Over 66.5

-112

Under 66.5

-112

Jauan Jennings (49ers)

Over 54.5

-112

Under 54.5

-112

Christian McCaffrey (49ers)

Over 40.5

-112

Under 40.5

-112

Tyler Warren (Colts)

Over 36.5

-112

Under 36.5

-112

Michael Pittman Jr. (Colts)

Over 31.5

-112

Under 31.5

-112

Josh Downs (Colts)

Over 27.5

-112

Under 27.5

-112

Kendrick Bourne (49ers)

Over 25.5

-112

Under 25.5

-112

Alec Pierce (Colts)

Over 19.5

-112

Under 19.5

-112

Jonathan Taylor (Colts)

Over 19.5

-112

Under 19.5

-112

Demarcus Robinson (49ers)

Over 16.5

-112

Under 16.5

-112

Kyle Juszczyk (49ers)

Over 7.5

-112

Under 7.5

-112

Rushing Yards

Jonathan Taylor (Colts)

Over 96.5

-112

Under 96.5

-112

Christian McCaffrey (49ers)

Over 61.5

-112

Under 61.5

-112

Brian Robinson Jr. (49ers)

Over 22.5

-112

Under 22.5

-112

Brock Purdy (49ers)

Over 11.5

-112

Under 11.5

-112

Ameer Abdullah (Colts)

Over 9.5

-112

Under 9.5

-112

Philip Rivers (Colts)

Over 0.5

+220

Under 0.5

-303

Passing Yards

Brock Purdy (49ers)

Over 248.5

-112

Under 248.5

-112

Philip Rivers (Colts)

Over 160.5

-112

Under 160.5

-112

Micro betting is an exciting way to wager on the NFL. There are a huge range of live lines and it’s a simple case of predicting what is going to happen next. Field Goal Outcome, Next Play Result and Next Drive Result are often among the options.

Colts Have Taken Seven Wins From Last Ten Home Outings

The Colts are 7-3 in their last 10 home games, putting up 27.70 points on average and giving up 21.00.

The Niners are riding three straight road wins. They own a 6-4 mark in their past 10 road games, posting 24.50 points per contest while yielding 24.30.

Last 10 Games		W-L	P	PF	PA	O46.5	U46.5
Colts Home Stats		7-3	48.70	27.70	21.00	6	4
49ers Away Stats		6-4	48.80	24.50	24.30	6	4

• W-L = Wins-Losses
• P = Avg. Points
• PF = Avg. Points For
• PA = Avg. Points Against
• O46.5 = Games Over 46.5 Points
• U46.5 = Games Under 46.5 Points

Latest regular season and playoff games stats.

San Francisco 49ers Stats

Indianapolis Colts Stats

Moneyline

• 7 wins and 3 defeats in the last 10 games
• 6 wins and 4 defeats in the last 10 games on the road

Moneyline

• 5 wins and 5 defeats in the last 10 games
• 8 wins and 2 defeats in the last 10 home games

Point Spread

• -5.5 Betting Line: Have covered the spread in 6 of the last 10 games
• -5.5 Betting Line on the Road: Have covered the spread in 3 of the last 10 games on the road

Point Spread

• +5.5 Betting Line: Have covered the spread in 8 of the last 10 games
• +5.5 Betting Line at Home: Have covered the spread in 9 of the last 10 home games

Total Points

• Game Totals: An average of 48.20 pts in the previous 10 games
• Game Totals on the Road: An average of 48.80 pts in the previous 10 games on the road
• Over 46.5: Covered in 6 of the previous 10 games
• Over 46.5 on the Road: Covered in 6 of the previous 10 games on the road
• Team Totals: Have scored an average of 26.40 pts and allowed 21.80 pts in the last 10 games
• Team Totals on the Road: Have scored an average of 24.50 pts and allowed 24.30 pts in the last 10 games on the road

Total Points

• Game Totals: An average of 48.90 pts in the previous 10 games
• Game Totals at Home: An average of 49.30 pts in the previous 10 home games
• Over 46.5: Covered in 6 of the previous 10 games
• Over 46.5 at Home: Covered in 6 of the previous 10 home games
• Team Totals: Have scored an average of 26.90 pts and allowed 22.00 pts in the last 10 games
• Team Totals at Home: Have scored an average of 28.80 pts and allowed 20.50 pts in the last 10 home games

Game Stats

Last 10 Games

• Total Yards: Gained 338.70 Yds. Allowed 354.90 Yds
• Rushing Yards: Gained 106.10 Yds. Allowed 102.30 Yds
• Passing Yards: Gained 232.60 Yds. Allowed 252.60 Yds
• Total Touchdowns: Scored 2.90 TD. Allowed 2.70 TD
• Rushing Touchdowns: Scored 1.20 TD. Allowed 0.70 TD
• Passing Touchdowns: Scored 1.70 TD. Allowed 2.00 TD
• Total 1st Downs: Picked up 22.10. Allowed 20.70
• Total Turnovers: Committed 1.10. Committed by opponents 1.10
• Total Penalties: Committed 4.90. Committed by opponents 6.10
• Penalty Yards: Lost 30.50 Yds. Gained 43.00 Yds

Game Stats

Last 10 Games

• Total Yards: Gained 341.60 Yds. Allowed 351.90 Yds
• Rushing Yards: Gained 125.40 Yds. Allowed 94.80 Yds
• Passing Yards: Gained 216.20 Yds. Allowed 257.10 Yds
• Total Touchdowns: Scored 3.30 TD. Allowed 2.10 TD
• Rushing Touchdowns: Scored 1.40 TD. Allowed 1.10 TD
• Passing Touchdowns: Scored 1.60 TD. Allowed 1.00 TD
• Total 1st Downs: Picked up 20.60. Allowed 22.10
• Total Turnovers: Committed 1.30. Committed by opponents 1.20
• Total Penalties: Committed 5.50. Committed by opponents 6.20
• Penalty Yards: Lost 47.50 Yds. Gained 52.00 Yds

Last 10 Games on the Road

• Total Yards: Gained 343.80 Yds. Allowed 362.30 Yds
• Rushing Yards: Gained 94.30 Yds. Allowed 115.40 Yds
• Passing Yards: Gained 249.50 Yds. Allowed 246.90 Yds
• Total Touchdowns: Scored 2.70 TD. Allowed 2.80 TD
• Rushing Touchdowns: Scored 0.80 TD. Allowed 0.80 TD
• Passing Touchdowns: Scored 1.90 TD. Allowed 2.00 TD
• Total 1st Downs: Picked up 21.60. Allowed 21.00
• Total Turnovers: Committed 1.10. Committed by opponents 1.10
• Total Penalties: Committed 6.90. Committed by opponents 6.20
• Penalty Yards: Lost 47.50 Yds. Gained 42.50 Yds

Last 10 Home Games

• Total Yards: Gained 393.80 Yds. Allowed 324.20 Yds
• Rushing Yards: Gained 175.00 Yds. Allowed 106.60 Yds
• Passing Yards: Gained 218.80 Yds. Allowed 217.60 Yds
• Total Touchdowns: Scored 3.30 TD. Allowed 2.50 TD
• Rushing Touchdowns: Scored 1.60 TD. Allowed 1.30 TD
• Passing Touchdowns: Scored 1.40 TD. Allowed 1.10 TD
• Total 1st Downs: Picked up 21.90. Allowed 21.10
• Total Turnovers: Committed 0.40. Committed by opponents 1.40
• Total Penalties: Committed 6.30. Committed by opponents 5.20
• Penalty Yards: Lost 50.30 Yds. Gained 51.90 Yds

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