Two teams headed in opposite directions meet Monday in Indianapolis when the Colts (8-6) losers of four straight take the field fighting for their playoff lives against the San Francisco 49ers (10-4) who have won four in a row.
Head Coach Kyle Shanahan and the Niners now control their fate in their pursuit of the NFC West crown and the top overall seed in the NFC. The scary part for the rest of the NFC is San Francisco is just now getting healthy having overcome a variety of injuries to key personnel on both sides of the ball.
The Colts, on the other hand, started the season 8-2 and were competing for the best record in the AFC, but now are in a full scramble as they sit outside a playoff spot. Phillip Rivers is now under center for his second start since returning from retirement. Last week was his first game in 1800 days. He completed 18-27 passes for 120 yds with one touchdown pass and one interception.
Christian McCaffrey: MVP Candidate
Christian McCaffrey has been the All-Pro running back San Francisco had to have if they were to survive the plethora of injuries that have plagues them this season. has avoided the injury bug. His season quietly borders on historic:
- 1,742 scrimmage yards this season (922 rushing / 820 receiving)
- Seeking his 2nd career season (2019 with CAR) with 1,000+ rushing yards & 1,000+ receiving yards (1999 Marshall Faulk & 1985 Roger Craig are the only other players to achieve this feat)
- With 58 scrimmage yards, McCaffrey would become the 5th player in NFL history with 1,800+ scrimmage yards in five seasons, joining Hall-of-Famers Walter Payton (7), LaDainian Tomlinson (5), Marshall Faulk (5) and Emmitt Smith (5)
Lets take a deeper dive into this week’s matchup between the 49ers and the Colts.
NBC Sports has all the latest info and analysis you need, including how to tune in for kickoff, odds from DraftKings, player news and updates courtesy of Rotoworld, and of course our predictions and best bets for the game from our staff of experts.
Game Details and How to watch the 49ers vs. Colts live Monday
- Date: Monday, December 22, 2025
- Time: 8:15PM EST
- Site: Lucas Oil Stadium
- City: Indianapolis, IN
- Network/Streaming: ESPN
Want to check out the other games on the NFL schedule this week? We’ve got you covered at NBC Sports with all the matchup, venue, game-time and TV/streaming info so you won’t miss any of the action!
Game Odds: 49ers at Colts
The latest odds as of Sunday courtesy of DraftKings:
- Moneyline: San Francisco 49ers (-270), Indianapolis Colts (+220)
- Spread: 49ers -5.5
- Total: 46.5 points
This game opened at 49ers -5.5 with the Game Total set at 45.5.
Be sure to check out DraftKings for all the latest game odds & player props for every matchup this week on the NFL schedule!
Quarterback Matchup: San Francisco at Indianapolis
- 49ers Starting QB: Brock Purdy
Last Game: 12/14 vs. Tennessee - 23-30, 295yds, 3TDs, 0INTs, Sacked 2 times, 7 carries for 44yds rushing
Season: 6GP, 129-190, 1442yds, 12TDs, 7INTs, Sacked 6 times, 23 carries for 87yds rushing
- Colts Starting QB: Phillip Rivers
Last Game: 12/14 at Seattle - 18-27, 120yds, 1 TD, 1INT, Sacked 1 time, 1 carry for -5yds rushing
Season: 1GP, 18-27, 120yds, 1 TD, 1INT, Sacked 1 time, 1 carry for -5yds rushing
49ers at Colts: Team Stats and Betting Trends
- Jonathan Taylor leads the NFL with 18 scrimmage TD this season
- With 2 TD, Taylor would become the 6th player in NFL history to have multiple
seasons with 20+ TD, joining LaDainian Tomlinson, Shaun Alexander, Marshall
Faulk, Priest Holmes and Emmitt Smith - The 49ers are 8-5-1 ATS this season
- The Colts are 7-5-2 ATS this season
- The OVER has cashed 8 times in the 49ers’ 14 games (8-5-1)
- The OVER has cashed 7 times in the Colts’ 14 games (7-7)
49ers Player Injuries
- WR Ricky Pearsall (ankle) has been declared OUT of Monday Night’s game
- LB Nick Martin (concussion) has been placed on the IR and has thus been declared OUT of Monday Night’s game
- CB Renardo Green (neck) has been declared OUT of Monday Night’s game
Colts Player Injuries
- QB Anthony Richardson (orbital) is eligible to be activated off the IR
- WR Anthony Gould (foot) has been declared OUT of Monday Night’s game
- LT Bernhard Raimann (elbow) has been declared OUT of Monday Night’s game
- CB Sauce Gardner (calf) is listed as questionable for Monday Night’s game
- S Daniel Scott (knee) is eligible to be activated off the IR
Rotoworld Best Bets
Please bet responsibly. If you or someone you know has a gambling problem, call the National Gambling Helpline at 1-800-522-4700.
Our model calculates projections around each moneyline, spread and over/under bet for every game on the NFL calendar based on data points like past performance, player matchups, stadium information and weather forecasts.
Once the model is finished running, we put its projection next to the latest betting lines for the game to arrive at a relative confidence level for each wager.
Best bets our model is projecting for this week’s game between the 49ers and the Colts
- Moneyline: Rotoworld Bet is staying away from a play on the Moneyline.
- Spread: Rotoworld Bet is recommending a play ATS on the San Francisco 49ers -5.5.
- Total: Rotoworld Bet is leaning towards a play on the UNDER on the Game Total of 45.5.
Rotoworld has you covered with all the latest betting info & tools for NFL with player news, game predictions, player props, futures, and trends!
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● Jay Croucher (@croucherJD)
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