The San Francisco 49ers — often called the 49ers or Niners — are one of the NFL’s most storied franchises. In Week 16 of the 2025 NFL season, the SF 49ers face the Indianapolis Colts (Colts) in a crucial 49ers game tonight on Monday Night Football that could impact playoff positioning for both teams.
49ers Schedule & Game Info
The 49ers schedule shows a strong 10-4 record as they travel to face the Colts at Lucas Oil Stadium in Indianapolis. This Niners vs Colts matchup kicks off at 8:15 p.m. ET as part of what time does Monday Night Football start tonight.
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Game: Niners vs Colts
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Kickoff: 8:15 p.m. ET (Tonight)
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Network: ESPN / ABC
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Week: 16 49ers game
This 49er game is a big test for both clubs — San Francisco seeks NFC West dominance while Indianapolis fights to stay in the AFC playoff hunt.
Key Storylines: 49ers vs Colts Predictions
Experts describe this 49ers vs Colts prediction as a competitive battle:
Predictions & Odds
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Many analysts have the 49ers favored, though some previews suggest the Colts could stay close and cover the spread.
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Some projections lean toward Colts keeping the game tight despite San Francisco’s stronger record.
This fuels strong Colts vs 49ers predictions chatter on social media and betting circles ahead of kickoff.
49ers Injury Report & Players to Watch
49ers Injury News
The 49ers injury report shows key absences and roster changes heading into the game:
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WR Ricky Pearsall is officially OUT with knee/ankle issues.
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CB Renardo Green will not play due to a neck injury.
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Yetur Gross-Matos has been activated from IR and could contribute.
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Eli Apple and veteran Eric Kendricks were elevated for added depth.
Kyle Shanahan, the 49ers coach, will rely on his depth to manage both offensive and defensive schemes.
49ers Players
San Francisco’s roster features several standout performers:
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Christian McCaffrey — elite RB and consistent offensive weapon.
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Brock Purdy — quarterback leading the offense with strong recent performances as the Niners strive for playoff seeding.
(Note: Fred Warner is out with a season-ending injury.)
Colts Roster & Key Contributors
Colts Players
The Indianapolis Colts also field notable names:
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Zaire Franklin — veteran linebacker anchoring the Indy defense.
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Philip Rivers, the veteran signal-caller, has resumed starting duties in place of injured QB Anthony Richardson.
Despite recent struggles, the Colts remain capable of making this Colts vs 49ers matchup close.
Colts Football Context & Schedule
The Colts schedule has presented ups and downs this season. After showing playoff potential earlier in 2025, Indianapolis has endured a late stretch of losses, making this Colts game tonight especially meaningful for postseason hopes.
Brian Robinson Jr., Stats & Impact
While Brian Robinson Jr. plays for another NFL team (the Washington Commanders) and not the 49ers or Colts, his yardage and NFL production remain part of broader league conversations about running back usage and fantasy football.
Brian Robinson stats this season reflect solid contributions — though his team context differs from the 49er game.
Who Plays Monday Night Football Tonight?
Tonight’s MNF tonight time showdown features:
San Francisco 49ers vs Indianapolis Colts — a pivotal late-season matchup with implications in both conferences.
This 49ers game today is one of the most talked-about matchups of the week among NFL fans and analysts.
Final 49er vs Colts Prediction
Overall, analysts expect:
49ers to edge out Colts due to depth and recent form.
Colts to stay competitive, possibly covering in a tighter scoreline.
Betting models show mixed confidence — so this 49ers vs Colts prediction isn’t a guaranteed blowout.
Whether you’re tracking the 49er game, Colts football, or planning watch parties in Indianapolis or across the country, tonight’s MNF clash delivers high stakes and big excitement.
Conclusion
The 49ers vs Colts matchup blends playoff intrigue and compelling storylines from both the 49ers and Indianapolis camps. With dynamic players, evolving injuries, and playoff pressure mounting, this Week 16 49er game is must-watch NFL drama.
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