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 Colts lost to the Seattle Seahawks, 18-16, in their last game.
The Colts’ Philip Rivers went 18-for-27 for 120 yards versus the Seahawks, with one TD and one INT.
Last time around, the 49ers defeated the Tennessee Titans, with 37-24 being the final score.
Colts vs 49ers betting information
NFL odds courtesy of BetMGM Sportsbook. Odds updated Monday at 1:07 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 pointsColts betting insightsAt home this season, Indianapolis is 6-1 overall and 4-3 against the spread.The Colts are 8-6-0 against the spread this year.The Colts have a perfect 1-0 ATS record when playing as at least 5.5-point underdogs.Indianapolis has gone over the total in four of seven games at home this season.Games involving Colts have hit the over seven times this year.Colts leadersRivers: 120 PASS YDS / 120.0 YPG / 66.7% / 1 TD / 1 INTJonathan Taylor: 272 CAR / 1,443 YDS / 103.1 YPG / 16 TD / 38 REC / 318 YDS / 22.7 YPG / 2 TDDJ Giddens: 18 CAR / 66 YDS / 16.5 YPG / 0 TDAlec Pierce: 39 REC / 785 YDS / 65.4 YPG / 2 TDMichael Pittman Jr.: 72 REC / 725 YDS / 51.8 YPG / 7 TDTyler Warren: 63 REC / 718 YDS / 51.3 YPG / 4 TDColts vs 49ers 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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