The Indianapolis Colts (8-6) host the San Francisco 49ers (10-4) for Week 16 Monday Night Football on December 22. Kickoff from Lucas Oil Stadium in Indianapolis, Ind., is set for 8:15 p.m. ET. MNF will broadcast on ESPN and ABC.
The 49ers are 5.5-point favorites over the Colts on the spread (49ers -5.5); the game total is 46 points. The 49ers are -210 favorites on the moneyline while the Colts are +210 home underdogs.
Below, you can find our 49ers vs Colts picks for Monday Night Football, which include predictions for the spread, moneyline, game total and two player props.
49ers vs Colts Picks & Predictions
| Game | Time (ET) | Best Bet |
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  | 8:15 p.m. | |
| 8:15 p.m. | |
| 8:15 p.m. | |
| 8:15 p.m. | |
| 8:15 p.m. | |
Specific betting recommendations come from the sportsbook offering preferred odds as of writing. Always shop for the best price using our NFL Odds page, which automatically surfaces the best lines for every game. | ||
Monday Night Football Odds
- 49ers vs Colts Moneyline: 49ers -260, Colts +210
- 49ers vs Colts Spread: 49ers -5.5, Colts +5.5
- 49ers vs Colts Total: 46
49ers vs Colts odds via bet365
49ers vs Colts Spread Prediction
By Billy Ward
While switching to 44-year-old grandfather Philip Rivers at quarterback obviously isn’t ideal for the Colts, he was surprisingly acceptable in his NFL return last week.
Rivers completed two-thirds of his passes – albeit for just 4.4 yards per attempt – while the Colts put up 16 points against the Seahawks. Those aren’t great numbers, obviously, but he mostly avoided negative plays — he had one sack and one interception — while keeping the Colts competitive against the league’s No. 1 defense by DVOA.
Tonight, Rivers and the Colts get a much easier opponent in the 49ers, who rank 25th in DVOA and dead last in adjusted sack rate. Rivers should have a mostly clean pocket to operate in, and with the 49ers also ranking 29th in adjusted line yards, the Colts should get plenty of rushing production from Jonathan Taylor.
The Colts' running game should, at a minimum, be able to kill the clock and keep things close, especially when paired with the Colts 12th-ranked defense by DVOA. I’m not sure it will be enough to win a close game against San Francisco, but with the spread rising all the way to 5.5 points it should be enough to cover.
The best line is -105 at FanDuel at the time of writing, but given the movement throughout the weekend there’s an outside shot we get Colts +6 points before kickoff, so consider holding out on your bet until closer to game time.
Pick: Colts +5.5 (-110); monitor for +6
49ers vs Colts Moneyline Pick
I like the Colts — the Philip Rivers Christmas miracle we've all been waiting for is here.
The 49ers have a bottom-eight defense — both against the run and pass — by DVOA. To me, the spread for this game is just way off with the 49ers as 5-6-point favorites; my numbers — which are heavily roster oriented, not just outcome — have the Colts favored in this spot.
DeForest Buckner is back for the Colts tonight, which is a significant addition as he's their best — and most important — defensive player. Yes, Charvarius Ward and Sauce Gardner are sidelined — but can Brock Purdy make the Colts pay? Ricky Pearsall is out and the 49ers' receivers just haven't been able to hurt teams down the field.
The Colts are No. 1 defending inside runs while the 49ers are 31st in EPA per play on their outside runs. San Francisco hasn't run the ball well this season generally so Indianapolis should be able to keep that aspect of the game in check.
And don't forget something we've discussed all season: the 49ers defense has been decimated by injuries — there's not much talent there and they aren't generating much pressure. Rivers is going to have a totally different experience going from a tough Seahawks defense to this version of the 49ers. He should have much more time to operate.
Pick: Colts Moneyline (+210)
49ers vs Colts Over/Under Pick
When Philip Rivers said in his press conference that the Colts were going to run the ball with volume and play defense, he wasn’t lying. They are going to do everything they can tonight to shorten this game against the 49ers, and they have a pretty good shot of being able to do so.
With the Colts calling run plays at 33% over expectation on first downs last week, the gameplan is clear — against a defense ranking 25th in rush defense DVOA, Indy should actually be able to sustain some drives. This will bleed the clock and help keep Brock Purdy and company off the field.
The cliche of keeping the opposing offense off the field doesn’t actually translate to wins but it does, however, result in fewer points being scored.
With Indianapolis failing to generate a single explosive offensive play last week, it’s highly unlikely it can score without taking a significant chunk of time off the clock.
The Colts defense is very good against the run, allowing just 3.8 yards per attempt to opposing running backs and even more impressively, only two quarterbacks have averaged over eight yards per pass attempt against them this season.
With the energy of the home crowd behind them, I like the their chances of keeping them in this game in a low-scoring affair on Monday night.
Pick: Under 46.5 (-115)
49ers vs Colts Player Props: Michael Pittman
By Derek Carty
THE BLITZ is forecasting 5.42 receptions for Michael Pittman tonight.
The oddsmakers' implied projection is 3.70 receptions, so I believe there is some value here. If you take the over, you’d be projected to win 72% of the time, resulting in a 52% ROI with expected value of $51.79 (based on a $100 wager). Pittman has gone over 3.5 receptions in 10-of-14 games this season.
This play is good down to at least -165.
Pick: Michael Pittman Over 3.5 Receptions (+112; bet to -165)
49ers vs Colts Anytime Touchdown Pick
By Chris Raybon
Jauan Jennings has been on a scoring tear of late, logging four touchdowns in his last three games. His emergence in the 49ers' passing attack has coincided with the return of Brock Purdy.
Purdy has been targeting both Jennings and George Kittle more than backup Mac Jones; Christian McCaffrey has also been getting less looks in the passing game — which is good news for Jennings here. Jennings has scored on 12.1% of his targets from Purdy compared to just 7.3% from Jones.
The Colts have one of the worst defenses against wide receivers as well; they'll be without Sauce Gardner and Charvarius Ward for this game, which is notable because that duo has not allowed a touchdown over 383 coverage snaps.
Jennings will also have less competition on his own team with Ricky Pearsall ruled out.
Pick: Jauan Jennings Anytime Touchdown Scorer (+150)
