Colts vs. Rams Final Score Prediction for NFL Week 4 (Can Los Angeles Win at Home?)

The Rams are favored at home, but can they cover?

Los Angeles Rams coach Sean McVay is 90-58 at home in his coaching career. / Kirby Lee-Imagn Images

Just like everyone expected, the Indianapolis Colts are 3-0 in the 2025 season and looking to take complete control of the AFC South in Week 4. 

Daniel Jones and Jonathan Taylor have captained a surprisingly elite offense (tied for first in EPA/Play), but the Colts are road underdogs in Week 4 against Sean McVay’s Los Angeles Rams.

The Rams are coming off a brutal loss against the Philadelphia Eagles in Week 3, as they blew a double-digit lead and had a last-second field goal blocked to secure the loss. Can L.A. bounce back as a favorite on its home field? 

This season, the SI Betting team is sharing a final score prediction for every game as a fun way to help bettors decide on spread and total bets. 

Using the latest odds and analysis from the SI team, here’s my prediction for the score of the Colts vs. Rams clash on Sunday. 

Colts vs. Rams Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• Colts +3.5 (-105)
• Rams -3.5 (-115)

Moneyline

• Colts: +160
• Rams: -192

Total

• 49.5 (Over -115/Under -105)

This spread has moved in favor of the Colts after opening up with the Rams as 4.5-point favorites. It’s worth noting that the Rams are just 24-26-3 against the spread when favored at home in the Sean McVay era. 

Meanwhile, Indy is the only team that is 3-0 against the spread so far in 2025.  

Colts vs. Rams Final Score Prediction

Earlier this week, SI’s NFL betting insider Iain MacMillan shared his favorite bet for this game in his Road to 272 column – where he picks every game, every week: 

It's time for us football fans to start believing in the Colts. Sure, a three-game sample size is still small, but they've been so dominant offensively that it's hard to ignore at this point. Their metrics are right up there with the Ravens and Bills, in their own category compared to the rest of the NFL.

The most elite offenses in the NFL are the Bills, Ravens, and Colts, as everyone predicted! pic.twitter.com/SJNXlK6IsN

— Iain MacMillan (@IainMacBets) September 22, 2025

The Colts also rank second in the NFL in Net Yards per Play at +1.6, one spot above their Week 4 opponent, the Los Angeles Rams. In terms of advanced metrics, they're slightly better offensively than the Rams, but Los Angeles has a small defensive advantage.

Any team with these close of numbers shouldn't have a spread north of a field goal. These odds are leftovers of offseason projections of both clubs. If you think you've seen enough of the Colts to consider them a legitimately good football team, there's a clear answer for which side you should back.

I understand why MacMillan believes in the Colts to cover – especially with this spread sitting at 3.5 – but the Rams are 90-58-0 at home in the Sean McVay era.

At some point, Daniel Jones and the Colts are going to regress a little bit on the offensive end, and I could see it happening against a top-10 defense like the Rams. 

I’ll back L.A. to win a close one on Sunday.

Final Score Prediction: Rams 23, Colts 21

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Odds refresh periodically and are subject to change.

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