Dec 22, 2025 8:15 PM EST

Week 16

San Francisco

8-6

Indianapolis

-6 (-110)o46½ (-110)

ESPN, 206

MATCHUP PREDICTION ODDS PLAYER PROPS GAME PROPS INJURIES WEATHER

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San Francisco 49ers vs Indianapolis Colts Picks

Updated:Dec 18, 2025 1:46 AM EST

The upcoming NFL Monday night football game on December 22, 2025, features the San Francisco 49ers visiting the Indianapolis Colts at Lucas Oil Stadium in Indianapolis, IN. This highly anticipated Week 16 matchup promises an exciting contest as both teams vie for crucial regular season wins. The game will be broadcast on ESPN, giving fans plenty of access to catch all the action live.

Our expert picks and predictions favor the San Francisco 49ers to win with a predicted score of 25-20 against the Colts. The model suggests taking the Indianapolis Colts +6.5 on the point spread, which holds a solid 55.6% cover percentage and an EV of 3.2%, making it a smart betting choice. Additionally, the total points are expected to stay under 46.5, with a 53.9% hit rate and a positive expected value of 2.7%.

In recent games, our prediction model has been profitable, especially in the point spread market, winning more than half of the last 10 games. This solid track record enhances confidence in our picks and betting tips for this matchup. Bettors can leverage these insights to make informed decisions and increase their chances of success. For more expert analysis and NFL picks, check out our detailed NFL picks and predictions. Ready to bet smarter? Start your OddsTrader Turbo subscription now or place your bet with a U.S. regulated sportsbook and profit off the edge.

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ODDS PICKS PLAYER PROPS FUTURES PLAYER FUTURES INJURIES WEATHER RANKINGS STANDINGS

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This Week

Last Week

Personalize your notifications and get updates on the teams, players or events you care about most. THU 12/188:15 PM L.A. Rams 11-3 45% +2 -114BetRivers
Seattle 11-3 55% -1½ -108FanDuel
Personalize your notifications and get updates on the teams, players or events you care about most. SAT 12/205:00 PM Philadelphia 9-5 15% -6½ -109Caesars
Washington 4-10 85% +6½ -110Caesars
Personalize your notifications and get updates on the teams, players or events you care about most. SAT 12/208:20 PM Green Bay 9-4-1 54% +1½ -134Caesars
Chicago 10-4 46% +1½ -120FanDuel
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM Buffalo 10-4 57% -10 -115Bet365
Cleveland 3-11 43% +10½ -114Caesars
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM N.Y. Jets 3-11 12% +4½ -107Caesars
New Orleans 4-10 88% -4½ -110Bet365
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM Minnesota 6-8 51% -2½ -122FanDuel
N.Y. Giants 2-12 49% +3 -113Caesars
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM Tampa Bay 7-7 13% -3 -105BetMGM
Carolina 7-7 87% +3 -110Bet365
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM Kansas City 6-8 14% -3 -110Caesars
Tennessee 2-12 86% +3 -105Bet365
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM L.A. Chargers 10-4 58% +2½ -110Caesars
Dallas 6-7-1 42% -2 -110Bet365
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/211:00 PM Cincinnati 4-10 34% -4 -110Bet365
Miami 6-8 66% +4½ -110BetRivers
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/214:05 PM Atlanta 5-9 73% -2½ -115FanDuel
Arizona 3-11 27% +3 -113Caesars
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/214:05 PM Jacksonville 10-4 43% +3 -105FanDuel
Denver 12-2 57% -3 -110Bet365
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/214:25 PM Pittsburgh 8-6 94% +7 -109Caesars
Detroit 8-6 6% -6½ -120FanDuel
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/214:25 PM Las Vegas 2-12 58% +14½ -115BetMGM
Houston 9-5 42% -14 -108BetRivers
Personalize your notifications and get updates on the teams, players or events you care about most. SUN 12/218:20 PM New England 11-3 31% +3 -113Caesars
Baltimore 7-7 69% -2½ -121SugarHouse
Personalize your notifications and get updates on the teams, players or events you care about most. MON 12/228:15 PM San Francisco 10-4 16% -6 -110Bet365
Indianapolis 8-6 84% +6½ -110BetMGM

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