Our projection model predicts the Indianapolis Colts will beat the San Francisco 49ers on Monday, Dec. 22 at 8:15 p.m. ET. For a complete projection on the game at Lucas Oil Stadium, which includes our prediction on the spread, over/under, and final score, keep reading.
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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 record against the spread this season.
- The Colts are 8-6-0 ATS this season.
- San Francisco has won each of its two games this season when playing as at least 5.5-point favorites.
- Indianapolis has won its only game this year when playing as at least 5.5-point underdogs.
- In the 49ers' 14 games this season, the combined scoring has gone over the point total eight times.
- So far this season, seven out of the Colts' 14 games with a set over/under have gone over the point total.
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