49ers vs. Colts Odds, Picks, Predictions: How Our Experts Are Betting This NFL Sunday Night Football Spread

49ers vs. Colts Odds, Picks Predictions

Colts +3.5

Sean Koerner: With heavy rain and wind in the forecast for Sunday night, the Colts should have the edge if this matchup is decided in the trenches and the running game. They have one of the NFL's best running back trios, led by second-year standout Jonathan Taylor, and All Pro left guard Quenton Nelson is making what should be a massive return for Indianapolis.

The 49ers, meanwhile, will be without left tackle Trent Williams (doubtful) — a huge blow considering he's the key to their offensive line and run blocking. Plus, they just haven’t been able to find consistency running the ball with Elijah Mitchell and Trey Sermon.

The weather forcing a trench war is evening more cutting with Trey Lance out — the No. 3 overall pick would have likely played a huge role in the Niners' game plan.

The Colts run defense ranks first in Football Outsiders' DVOA, led by linebacker Darius Leonard and former 49er DeForest Buckner. The 49ers, meanwhile, will be without defensive tackles Maurice Hurst and Javon Kinlaw, the latter of whom they drafted in the first round last season to replace Buckner. Normally their absences wouldn’t matter too much, but in a matchup that will likely be decided in the trenches, it could have an impact.

I would be the Colts down to +3.

Colts +3.5

Raheem Palmer: The Colts have been playing solid football recently, winning two out of their last three games and probably should have won their Monday Night Football matchup against the Ravens if it weren't for a blocked field goal.

Nevertheless, I want to back the Colts against the 49ers, who have lost three straight games. I've never been big on trends, but road underdogs of six or fewer points are 25-9 (73.5%) against the spread (ATS) this season.

Trends aside, this feels like an ideal spot for Carson Wentz and the Colts, who face a 49ers defense that's really struggled in the secondary They're just 26th in Dropback Success Rate (48.5%), and the loss of cornerback Jason Verrett in Week 1 is notable given the struggles of Emmanuel Moseley, Deommodore Lenoir and K’Waun Williams, who is returning from a calf injury.

It's tough to know what to expect from the 49ers offense with the possible return of Jimmy Garoppolo, who wasn't particularly great this season. Overall, this line is too high. And with my model making this game 49ers -2, I'll back the Colts at +3.5.

Colts +3.5

Brandon Anderson: As a diehard North Dakota State fan, I had this game circled on my calendar from the moment the schedule came out. I could never imagine as a kid growing up in Fargo that I could someday see my beloved Bison start at quarterback in the NFL — and this game meant a potential chance to see two NDSU signal callers opposite one another in primetime.

An actual dream come true!

Alas, it was not meant to be, because Lance is banged up and because Kyle Shanahan continues to stubbornly stick with Jimmy Garoppolo for far too long even though Shanahan clearly doesn’t trust him. And I gotta be honest — I’m starting to fade Shanahan overall. That’s typically been a good idea when he and the Niners are favored: Underdogs are 20-8-1 ATS against Shanahan, covering 71% of the time.

It's not going well.

The 49ers had their bye at the right time, with a chance to lick their early-season wounds and get healthy. That should help, but the Colts are starting to get healthy, too. Wentz has quietly played pretty well while Taylor and the run game have been terrific of late.

Indianapolis has an outstanding run defense, so that puts this game squarely on the shoulders of Garoppolo. And if Shanahan doesn’t trust Jimmy G, why should we?

The Colts have been absolutely miserable in the red zone while the 49ers have scored a touchdown on all but one trip. That sort of thing can doom a team even if it plays way better, but it also tends to regress over time. The Colts have played much better on the road, and they’ve been good in the second half. The longer this stays close, the better chance Indianapolis will have.

Under 42.5

Sean Koerner: I'm picking this under based on a lot of the same reasoning I like the Colts down to +3 — the weather should force both teams into a run-heavy game plan with key weapons like Trey Lance, George Kittle, T.Y. Hilton, Trent Williams and Braden Smith all expected to miss — both facts that favor the under.

Forty-three is a key numbers for totals, so it’s critical to bet it at that number if you have access to it, but I still like it down to 41.5 (shop for the best line here).

Kyle Juszcyk Over 1.5 Rec

Michael Arinze: The West Coast is preparing for what weather experts call a "bomb cyclone," and it's likely to impact Sunday night's game. Both teams could be facing wind gusts up to 20 mph and heavy rain throughout the game, which is a big reason why the total dropped from as high as 45.5 down to 42.5 as of writing.

As you'd expect, the passing props have been adjusted accordingly, but that doesn't mean both quarterbacks are just going to drop back and hand the ball off each time. While it might be difficult to throw the ball down the field, short passes should still be available as an option. That's why you should look to target Juszcyk to go over his prop of 1.5 receptions.

Juszcyk has caught at least two passes in his last four games and at least three passes in his previous three games. Since Week 3, he's been involved in at least 65% of the team's snaps.

Given the weather conditions, San Francisco is well-equipped to go with a heavy or 22 personnel grouping: Two running backs, two tight ends and one wide receiver. Per Sports Info Solutions, the 49ers are in this package 9% of the time, which is well above the 3% league average. As for the Colts, the data doesn't show any record of the team in this package much at all this season.

BetMGM lists Juszcyk's prop of 1.5 receptions at -145 odds as of writing. I'm comfortable playing it up to -155.