Our computer model predicts the Indianapolis Colts will defeat 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 scrolling.
Don't miss a touchdown this NFL season. Catch every score with NFL RedZone on Fubo. What is Fubo? Fubo is a streaming service that gives you access to your favorite live sports and shows on demand. Sign up today and watch seven hours of football from every NFL game every Sunday.
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)
Catch every NFL touchdown with NFL RedZone on Fubo.
Listen to the game on 107.5 The Fan
49ers vs. Colts Odds and Betting Info
- Spread favorite: 49ers (-4.5)
- Moneyline: 49ers (-235), Colts (+194)
- Total: 46 points
49ers vs. Colts Prediction
- Pick ATS: Colts (+4.5)
- Pick OU: Over (46)
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.
See how these predictions pan out and sign up for NFL RedZone on Fubo to catch every score on Sundays this fall.
49ers vs. Colts Betting Insights
- The 49ers have put together a 9-5-0 ATS record so far this year.
- The Colts have put together an 8-6-0 record against the spread this year.
- When playing as at least 4.5-point favorites this season, the 49ers have an ATS record of 3-0.
- Indianapolis has won each of its two games this season when playing as at least 4.5-point underdogs.
- In the 49ers' 14 games this season, the combined scoring has gone over the point total eight times.
- In the Colts' 14 contests this year, the combined scoring has gone over the point total seven times.
Looking for NFL tickets? Head to StubHub today and see your team live.