San Francisco (10-4) brings a four-game winning streak into a matchup with Indianapolis (8-6) on Monday, December 22, 2025 at Lucas Oil Stadium. The 49ers are the favorites in this one, with the spread sitting at 5.5 points. An over/under of 46 points has been set for the outing.
The 49ers won against the Tennessee Titans in their last game, 37-24.
Niners quarterback Brock Purdy went 23-for-30 for 295 yards, with three TDs and no INTs, versus the Titans.
The Colts lost to the Seattle Seahawks, 18-16, in their most recent game.
49ers vs Colts betting information
NFL odds courtesy of BetMGM Sportsbook. Odds updated Monday at 12:47 a.m. ET. For a full list of sports betting odds, access USA TODAY Sports Betting Scores Odds Hub.
Spread favorite: San Francisco (-5.5)Moneyline: San Francisco (-260), Indianapolis (+210)Total: 46 points49ers betting insightsIn away games, San Francisco is 6-2 overall and 6-2 against the spread.The 49ers are 9-5-0 against the spread this season.In games they have played as 5.5-point favorites or more, the 49ers have a perfect ATS record of 2-0.This year, in five of eight road games San Francisco has hit the over.49ers games have gone over the total eight times this season.49ers leadersPurdy: 1,442 PASS YDS / 240.3 YPG / 67.9% / 12 TD / 7 INT / 23 CAR / 87 RUSH YDS / 1 TDChristian McCaffrey: 259 CAR / 922 YDS / 65.9 YPG / 9 TD / 86 REC / 820 YDS / 58.6 YPG / 5 TDBrian Robinson Jr.: 81 CAR / 349 YDS / 24.9 YPG / 2 TD / 7 REC / 19 YDS / 1.4 YPG / 0 TDKendrick Bourne: 33 REC / 499 YDS / 45.4 YPG / 0 TDJauan Jennings: 44 REC / 495 YDS / 41.3 YPG / 7 TD49ers vs Colts game infoDate: Monday, December 22, 2025Time: 8:15 p.m. ETCity: Indianapolis, IndianaVenue: Lucas Oil StadiumTV channel: ESPNLive stream: Watch on Fubo (Regional restrictions may apply)
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