Indianapolis Colts vs. Los Angeles Rams early prediction: Expert picks for NFL Week 4, 2025

The Indianapolis Colts and Los Angeles Rams will meet in Week 4 of the NFL season at SoFi Stadium on Sunday, September 28, 2025, starting at 4:05PM ET.

Early simulations from Dimers' trusted NFL model favor the Rams as the most likely winner of this matchup.

For updates all week long, including best bets, player prop projections and touchdown probabilities, check out our interactive Colts vs. Rams predictions page.

Indianapolis vs. LA Rams early predictions

Leveraging trusted machine learning and analysis, we have simulated the Colts vs. Rams game 10,000 times as part of our NFL predictions coverage. Here are the latest insights:

• Straight up win probabilities: Colts 29%, Rams 71%
• Predicted final score: Colts 20-25 Rams
• Spread: Colts (+6.5) 57%, Rams (-6.5) 43%
• Total points (46.5): Over 50%, Under 50%

As of September 21, 2025, these Colts-Rams calculations and predictions reflect the latest data and insights available.

Colts vs. Rams Week 4 details

The NFL Week 4 matchup between the Rams and Colts at SoFi Stadium is scheduled for September 28, 2025.

• Who: Indianapolis Colts vs. Los Angeles Rams
• Date: Sunday, September 28, 2025
• Time: 4:05PM ET/1:05PM PT
• Venue: SoFi Stadium

Colts vs. Rams opening odds

We've researched the best betting odds across America for this Week 4 game, which are listed here:

• Spread: Colts +6.5 (-110), Rams -6.5 (-110)
• Moneyline: Colts +235, Rams -290
• Total: Over/Under 46.5 (-110/-110)

Odds may continue to move—track live changes via our NFL odds page.

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Conclusion

We predict the Rams, with a 71% win probability, will likely beat the Colts in Week 4 of the NFL season. Dimers.com will provide full game coverage closer to kickoff, so stay tuned for updates.

Enhanced by AI and automation, this article delivers quick, accurate insights on the Colts vs. Rams game, with human oversight maintaining high editorial quality. Our predictions are based on the latest data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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