Colts vs. Rams Prediction, Odds, Spread, Injuries, Trends for NFL Week 4

Iain MacMillan | Sep 23, 2025

Daniel Jones and the Colts are road underdogs against the Rams in Week 4. / Steve Roberts-Imagn Images

The Indianapolis Colts have emerged as the surprise of the season through the first three weeks. They're sitting at 3-0, but it's not just their record that's impressive, it's their complete dominance in two of those three games.

Now, it's time to find out just how legitimate the Colts are. They hit the road to take on the Los Angeles Rams in Week 4 action, which will serve as their toughest test to date.

Let's dive into the odds and my best bet for this interconference showdown.

Colts vs. Rams Odds, Spread, and Total

Odds via Caesars Sportsbook

Spread

• Colts +3.5 (-110)
• Rams -3.5 (-110)

Moneyline

• Colts +162
• Rams -195

Total

• OVER 49.5 (-110)
• UNDER 49.5 (-110)

Colts vs. Rams How to Watch

• Date: Sunday, Sept 28
• Game Time: 4:05 pm ET
• Venue: SoFi Stadium
• How to Watch (TV): FOX
• Colts Record: 3-0
• Rams Record: 2-1

Colts vs. Rams Betting Trends

• Colts are 4-2 ATS in their last six games
• The OVER is 5-1 in the Colts' last six games
• Rams are 7-3 ATS in their last 10 games vs. Colts
• Rams are 5-1 ATS in their last six games
• The OVER is 7-0 in the last seven meetings between these two teams
• Rams are 11-1 straight up in their last 12 games vs. AFC South opponents

Colts vs. Rams Injury Reports

Colts Injury Report

• Kenny Moore II, CB - Doubtful
• Alec Pierce, WR - Questionable
• Jaylon Jones, CB - IR
• Jaylon Carlies, LB - IR-R
• Hunter Wohler, IR - S

Rams Injury Report

• Nick Hampton, LB - Questionable
• Steve Avila, G - Questionable
• Ahkello Witherspoon, CB - IR
• Keir Thomas. LB - IR

Colts vs. Rams Key Player to Watch

• Jonathan Taylor, Running Back - Indianapolis Colts

All eyes are on the resurgence of Daniel Jones, but Jonathan Taylor has been the star of this team. He's averaging 5.6 yards per carry through the first three games, along with eight receptions for 93 yards and four total touchdowns. He has taken over as the betting favorite to win Offensive Player of the Year, which makes him a fascinating player to watch as the season marches on.

Colts vs. Rams Prediction and Pick

In this week's edition of the Road to 272 Bets, I broke down why I'm ready to buy in on the Colts:

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, their 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.

Pick: Colts +3.5 (-110) via Caesars

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Odds refresh periodically and are subject to change.

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You can check out all of Iain's bets here!