Photo: Ezra Shaw / Getty Images Sport / Getty Images
Which team is going to win on Monday, Dec. 22, when the Indianapolis Colts and San Francisco 49ers go head to head at 8:15 p.m. ET? Our projection system sides with the Colts. Check out our other projections below, where we break down the final score, spread, and over/under.
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49ers vs. Colts Game Info and TV Channel
- When: Monday, December 22, 2025 at 8:15 p.m. ET
- Where: Lucas Oil Stadium in Indianapolis, Indiana
- TV: ESPN
- Live Stream: Watch this game on Fubo (Regional restrictions may apply)
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Listen to the game on 107.5 The Fan
49ers vs. Colts Odds and Betting Info
- Spread favorite: 49ers (-5.5)
- Moneyline: 49ers (-258), Colts (+209)
- Total: 46.5 points
49ers vs. Colts Prediction
- Pick ATS: Colts (+5.5)
- Pick OU: Over (46.5)
Prediction:
Colts 24 - 49ers 23
Prediction derived from a team strength comparison algorithm. Multiple factors such as strength of wins and scoring margin are used to make this projection.
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49ers vs. Colts Betting Insights
- The 49ers have compiled a 9-5-0 ATS record so far this year.
- The Colts are 8-6-0 ATS this year.
- San Francisco has covered the spread when playing as at least 5.5-point favorites in two of two opportunities this season.
- Indianapolis has won its only game this year when playing as at least 5.5-point underdogs.
- The 49ers and their opponent have combined to go over the point total eight out of 14 times this season.
- The Colts and their opponent have combined to hit the over seven out of 14 times this year.
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