49ers vs Colts Week 16 Monday Night Football Betting Picks

The San Francisco 49ers will take on the Indianapolis Colts in a somewhat important Monday Night Football game. I’ll explain why this game matters, but it has less impact than most “playoff” games.

First, the 49ers clinched a playoff spot with the Detroit Lions’ loss to the Pittsburgh Steelers yesterday. They technically can still win the NFC West, but it’s highly unlikely. Instead, they’re playing for seeding.

The Colts aren’t technically eliminated from the playoffs at this point, but they more or less are. The chances they make the playoffs at this point are slim. They will also still technically be in contention with a loss in this game.

It’s a game that matters, but it also somehow doesn’t matter all that much. It’s a strange dynamic to explain.

Indianapolis featured one of the best offenses in the NFL throughout the season, but I don’t trust it with Philip Rivers in 2025. He returned last week against the Seattle Seahawks, and they posted only 16 points. They averaged .276 points per play, which is drastically lower than their .466 season average.

I don’t expect this team to get much better because Rivers isn’t truly working his way back into the game of football. He knows the offense, and I highly doubt the physical aspect is going to get better. Instead, this is essentially what the Colts are now.

San Francisco has dealt with a plethora of injuries throughout the season, but they’re getting healthier as the season progresses. Even with those injuries, they rank 12th in the NFL in points allowed (.349) per play. They’re giving up only 20.9 points per game this season.

On the other side, the 49ers have a good offense at this point, but I’m trusting the Colts' defense. Indianapolis ranks seventh in the league in points allowed (.331) per play. They’re giving up only 17.2 points per game at home this season.

The Colts are in a position where they know they aren’t likely to score a ton of points in their games. They’re going to need to lean more on their defense, and that was a defense that stepped up against Seattle last week.

Although I don’t fully trust the 49ers’ defense, I feel comfortable fading the Colts’ offense at this point. I also feel good about backing this Indianapolis defense.

Where to Bet: San Francisco 49ers & Indianapolis Colts under 46.5 points | -115 at FanDuel Sportsbook

2025 NFL Season Betting Record: 23-34