The Indianapolis Colts (8-6) take a four-game losing streak into a matchup with the San Francisco 49ers (10-4) on Monday, December 22, 2025 at Lucas Oil Stadium. San Francisco is a 5.5-point favorite in the game.
49ers vs. Colts game infoGame day: Monday, December 22, 2025Game time: 8:15 p.m. ETTV channel: ESPNLocation: Indianapolis, IndianaStadium: Lucas Oil StadiumLive stream: Watch this game on Fubo (Regional restrictions may apply)
Watch San Francisco 49ers vs. Indianapolis Colts on Fubo! (Regional restrictions may apply)
49ers vs. Colts odds & betting linesSpread favorite: San Francisco (-5.5)Moneyline: San Francisco (-267), Indianapolis (+217)Total: 46.5 points
NFL odds courtesy of BetMGM Sportsbook. Odds updated Friday at 10:55 p.m. ET. For a full list of sports betting odds, access USA TODAY Sports Betting Scores Odds Hub.
49ers vs. Colts recent matchupsIndianapolis is 2-0 versus San Francisco in the past two matchups between the two teams.Indianapolis has had the scoring advantage in those two matchups, totaling 56 points while San Francisco scored 41.49ers vs. Colts betting insightsSan Francisco is 9-5-0 against the spread so far this season. The 49ers have been listed the moneyline favorite 10 times this season, and they have put together a 9-1 record in those games. Indianapolis has an 8-6-0 record against the spread this season. The Colts’ record in games they’ve played as the underdog this year is 2-3.49ers scoring insightsThe 49ers are averaging fewer points at home (23.3) than on the road (25.5).On defense, San Francisco concedes more points at home (21.0 per game) than on the road (20.9), but barely.The 49ers are scoring 25.2 points per game in divisional matchups, which is a little better than their 24.2 average versus the rest of the league.San Francisco averages more points conceded in division games (23.0) than against the rest of the league (19.8).The 49ers’ defense has been wreaking havoc on opposing offenses over the last three contests, ranking best by allowing only 13.7 points per game. On the offensive side of the ball, they rank 10th in the NFL during that three-game period (27.7 points per game).Colts scoring insightsAt home, the Colts score 31.1 points per game, better than their 24.9 average away from home.Defensively, Indianapolis allows fewer points at home (18.3 per game) than away (25.0).On offense, the Colts are scoring 28.5 points per game in divisional matchups, which is slightly better than their 27.8 average outside the division.Indianapolis has allowed 22.5 points per game in the division, which is worse than its mark in non-division games of 21.3.In their past three games, the Colts are scoring 17.0 points per game (fourth-worst in NFL) and giving up 24.7 per game (19th).49ers injury report49ers:
Kurtis Rourke: Full Participation in Practice (Knee),
Ricky Pearsall: Did Not Participate In Practice (Knee),
Sam Okuayinonu: Limited Participation in Practice (Ankle),
Christian McCaffrey: Full Participation in Practice (NIR – Rest),
Nickolas Martin: Did Not Participate In Practice (Concussion),
Yetur Gross-Matos: Limited Participation in Practice (Hamstring),
Renardo Green: Limited Participation in Practice (Neck),
Jordan Elliott: Limited Participation in Practice (Knee),
Spencer Burford: Limited Participation in Practice (Knee),
Tatum Bethune: Limited Participation in Practice (Ankle),
Trent Williams: Full Participation in Practice (NIR – Rest)Colts injury reportColts:
Anthony Richardson: Limited Participation in Practice (Eye),
Bernhard Raimann: Did Not Participate In Practice (Elbow),
Germaine Pratt: Full Participation in Practice (Personal),
Alec Pierce: Full Participation in Practice (Achilles),
Quenton Nelson: Limited Participation in Practice (Wrist),
Anthony Gould: Did Not Participate In Practice (Foot),
Sauce Gardner: Did Not Participate In Practice (Calf),
Josh Downs: Full Participation in Practice (Personal),
DeForest Buckner: Full Participation in Practice (Neck),
Ameer Abdullah: Full Participation in Practice (Knee),
Grover Stewart: Did Not Participate In Practice (Rest),
Daniel Scott: Full Participation in Practice (Knee)
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