We’ve got a Monday Night Football clash that feels like a fever dream from 2020, but here we are in 2025. The San Francisco 49ers (10-4) are rolling into Lucas Oil Stadium to face the Indianapolis Colts (8-6), and yes, 44-year-old Philip Rivers will be under center for Indy. Let’s break down the matchups, odds, and best MNF player prop bets for our Colts vs. 49ers predictions.
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NFL Bets Today: Colts vs 49ers Predictions & Preview (12/22)
The Niners are road warriors this year (6-2 away from Levi’s), riding a four-game heater that has them looking like the NFC juggernaut we expected. Meanwhile, the Colts are in survival mode.
They’ve dropped four straight, after believing in a small Daniel Jones sample size and trading away a few integral future first-round draft picks to acquire Sauce Gardner, who is also injured. It’s been a nightmare scenario of events between both players’ injuries for the Colts. Now, after Jones’ injury a few weeks ago, it’s Rivers’ world, and we’re all living in it again.
Without Gardner, the Colts’ secondary could be exposed against a 49ers passing attack that is humming. Indy has allowed the 4th-most passing yards in the NFL. Some of that is because they are very stout against the run, ranking in the top third of the league in most defensive rushing metrics.
Colts vs 49ers Injury Report
The biggest injuries for Monday Night Football include:
- Sauce Gardner (IND) – OUT
- Daniel Jones (IND) – OUT
- Ricky Pearsall (SF) – OUT
Colts vs 49ers Odds
- Spread: 49ers -5.5 (-112)
- Moneyline: Colts +215
- Game Total (O/U): 46.5
How to Watch Colts vs 49ers
- TV: ESPN (Joe Buck, Troy Aikman), ABC (Simulcast)
- Streaming: Disney+, ESPN App, NFL+
- Kickoff: 8:15 p.m. ET
- Venue: Lucas Oil Stadium (Indy Home Game)
NFL LIVE PLAYER PROP ODDS
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Brock Purdy
SF
QB SF @ IND
Today
8:15 PM ET
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Philip Rivers
IND
QB SF @ IND
Today
8:15 PM ET
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NFL Expert Picks: Colts-49ers Best Player Prop Bets For Monday Night Football
Monday Night Football should be a blast, featuring studs like Christian McCaffrey and Jonathan Taylor. Check out some of the popular Monday Night Football props on Underdog:
PICK: Brock Purdy Higher Than 244.5 Pass Yards
Purdy is coming off a surgical 295-yard performance last week, and he’s got his favorite weapon, Christian McCaffrey, putting up video game numbers. CMC has already racked up 1,742 scrimmage yards and leads the team with 86 catches. Without Gardner to lock down one side of the field, Kyle Shanahan is going to hunt matchups all night.
PICK: Jauan Jennings Higher Than 54.5 Receiving Yards
Jenning has been a big help to Purdy. The SF receiver owns a 27% air yard share adn 18% target share in 2025. He’ll probably pick up a few extra looks without Pearsall in the fold.
PICK: Tyler Warren Higher Than 35.5 Receiving Yards
It was really ugly for Phillip Rivers last week. However, Warren saw six targets; he’s a big target, and he’s the best YAC guy on the Colts. I think Rivers will struggle again, but the Colts should be playing from behind, and Warren should get enough volume to be very competitive at this line.
Good luck, and enjoy Monday Night Football!
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