Jacksonville Jaguars vs. San Francisco 49ers early prediction: Expert picks for NFL Week 4, 2025

The Jacksonville Jaguars and San Francisco 49ers will meet in Week 4 of the NFL season at Levi's Stadium on Sunday, September 28, 2025, starting at 4:05PM ET.

Early simulations from Dimers' trusted NFL model favor the 49ers 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 Jaguars vs. 49ers predictions page.

Jacksonville vs. San Francisco early predictions

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

• Straight up win probabilities: Jaguars 33%, 49ers 67%
• Predicted final score: Jaguars 21-26 49ers
• Spread: Jaguars (+5.5) 54%, 49ers (-5.5) 46%
• Total points (48.5): Over 50%, Under 50%

As of September 21, 2025, these Jaguars-49ers figures and predictions reflect the latest data and insights available.

Jaguars vs. Niners Week 4 details

The NFL Week 4 game between the 49ers and Jaguars at Levi's Stadium is scheduled for September 28, 2025.

• Who: Jacksonville Jaguars vs. San Francisco 49ers
• Date: Sunday, September 28, 2025
• Time: 4:05PM ET/1:05PM PT
• Venue: Levi's Stadium

Jaguars vs. Niners opening odds

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

• Spread: Jaguars +5.5 (-110), 49ers -5.5 (-110)
• Moneyline: Jaguars +200, 49ers -245
• Total: Over/Under 48.5 (-110/-110)

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

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Conclusion

We predict the 49ers, with a 67% win probability, will likely beat the Jaguars 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 Jaguars vs. 49ers matchup, with human oversight maintaining high editorial quality. Our predictions are drawn from up-to-date data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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