The San Francisco 49ers, riding a four-game winning streak, face the struggling Indianapolis Colts on Monday Night Football with playoff implications on the line. San Francisco has clinched a postseason berth and eyes the NFC's top seed, while the Colts fight to stay alive in the wild-card race. Veteran quarterback Philip Rivers starts his second game for Indianapolis against Brock Purdy and the 49ers.
The San Francisco 49ers (10-4) travel to Lucas Oil Stadium in Indianapolis to take on the Indianapolis Colts (8-6) in Week 16's Monday Night Football matchup, scheduled for 8:15 p.m. ET on December 22, 2025. Broadcast on ESPN and ABC, with streaming available on Fubo, the game pits two teams on divergent paths: the 49ers have won four straight, including a 37-24 victory over Tennessee in Week 15, while the Colts have dropped four consecutive games, most recently falling 18-16 to Seattle.
For the 49ers, a win keeps them in contention for the NFC West title and the conference's No. 1 seed, controlling their destiny with remaining games against the Bears and Seahawks. They rank among the NFL's top four in third-down and passing offense despite injuries, and running back Christian McCaffrey nears a historic 1,000-1,000 rushing-receiving season with 922 rushing yards and 820 receiving yards through 14 games. Tight end George Kittle has scored four touchdowns in his last five games, and quarterback Brock Purdy is 5-1 against the spread this season.
The Colts, clinging to the eighth spot in the AFC, need a victory to maintain wild-card hopes, as a loss would nearly eliminate them and clinch spots for other contenders. They turn to 44-year-old Philip Rivers, who came out of retirement after Daniel Jones' Achilles injury; in his debut last week, Rivers completed 18 of 27 passes for 120 yards, one touchdown, and one interception. Running back Jonathan Taylor leads the NFL with 16 rushing touchdowns but has been held under 100 yards in each of the last four games. Indianapolis has dominated the series, winning the last five meetings and nine of the past 12 home games against San Francisco.
Injuries impact both sides: Colts cornerback Sauce Gardner is out with a calf injury, and offensive tackle Bernhard Raimann is inactive, while 49ers wide receiver Ricky Pearsall sits out due to knee and ankle issues. Odds list the 49ers as 4.5- to 5.5-point favorites with a total of 46 to 46.5 points, as projection models anticipate a high-scoring affair leaning over.
