Monday Night Football Picks: San Francisco 49ers vs Indianapolis Colts

by Mike Allen - 12/19/2025

The old man almost did it. I was front row at the sports bar and some Chiefs fans were upset they didn’t get to see their boys on the big screen. As it turned out, this was a good thing as Patrick Mahomes tore his ACL as the team was simultaneously eliminated from postseason contention.

Back to the big man, though; the elephant in the room, if you will. On less than a week’s notice, Philip Rivers traded a Friday night headset for his old #17 jersey and made his return to NFL action.

This was his first game back in five years and against a 10-3 at the time Seattle Seahawk team, mind you, with a ferocious defense. We were all pulling for him, but the better team locked in down the stretch and secured the victory.

Some, including myself, said the Seahawks were looking ahead to what became one of the greatest regular season NFL games I think I’ve ever seen on Thursday Night Football against their division rival Los Angeles Rams. We had the over 44 and it hit fairly easily with the final in overtime 38-37.

I mention this for a couple of reasons, one being I’m still high from that game and the other, for us not to get too excited about what was an inspired performance not only by Rivers but the entire Indianapolis Colts team.

I’m not sure, though, how hard they’ll be pushing it this week, as they will need a significant amount of help to make the playoffs. .

When you’re looking to fade a team who’s eliminated from potentially playing in the postseason, you want to beware of divisional opponents and stand-alone games like we have here on Monday Night Football.

With all that being said, maybe we look towards a total here as the Colts have one of the best run defenses in all of football, allowing just 3.7 yards per carry on the season, tying them with the aforementioned Seahawks for 1st in the NFL.

Let’s go ahead and check the betting odds for this late season strange matchup, and we can hopefully put together another Monday Night Football winner, fattening your bankroll for the upcoming Christmas games.

Doc’s Sports offers NFL expert picks for every game on our NFL predictions page.

San Francisco 49ers (-5.5) at Indianapolis Colts (+5.5)

This is right where we opened up. I am seeing some of the sharper books go ahead and move this line to (-6) for the Niners. So, if you like San Francisco, I would take them sooner rather than later.

Point Total: 46.5

I like the under in this game but 47 is the most key number as far as point totals are concerned. The books know that and many times, it can be a tell.

Moneyline Odds

49ers: -265

Colts: +210

San Francisco 49ers at Indianapolis Colts Betting Analysis

The key to victory in this game is essentially running the ball if you’re Indianapolis. Rivers or no Rivers, this has been the key to their success. If they don’t get triple digits on the ground, they won’t win this game.

If I were the 49ers’ defensive coordinator, Robert Salah, I’d make Rivers beat me over the top. Look, his arm strength wasn’t there 5 years ago when he retired, and it certainly isn’t there now.

The Colts will need Jonathan Taylor to have a stellar game, and he has regressed down the stretch this year. Why?

I’m not sure. It’s probably just wear and tear at this point. While Taylor leads the league in yards, touchdowns, and has only one fumble, he has also carried the ball more than any other back in the league.

I don’t see Indy scoring more than 20 points here, so you would think the under is in play, but the Niners are not a run-first team, and even if they were, it might not be a good idea against the Colts.

Brock Purdy has been lights out since his return from injury, and I expect San Francisco to try to make this game as much of a shootout as possible.

Give me the 49ers here to stack the box against Taylor, likely pick off a couple of Rivers’ passes, and pull away late. The potential for a backdoor cover by Indy is almost nonexistent.

San Francisco 49ers at Indianapolis Colts Betting Pick

Pick: San Francisco 49ers (-5.5)

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Monday Night Football Picks: San Francisco 49ers vs Indianapolis Colts

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