San Francisco 49ers vs Jacksonville Jaguars September 28th 2025

The Jacksonville Jaguars are set to visit the San Francisco 49ers in Week 4 of the 2025 NFL season. The game will take place at Levi’s Stadium in Santa Clara, California. Kickoff is scheduled for 4:05 PM on Sunday, September 28, and will be broadcast on FOX.

The Jaguars, led by head coach Liam Coen, have a 2-1 record this season. They are looking to improve their road performance after a loss away from home. Meanwhile, the 49ers, under head coach Kyle Shanahan, remain undefeated with a 3-0 record. The weather forecast predicts a mild day with clear skies, making for good playing conditions.

Jaguars vs 49ers Key Information

Sport: Football
Teams: Jacksonville Jaguars vs. San Francisco 49ers
Venue: Levi’s Stadium in Santa Clara, CA USA
Date: Sunday, September 28, 2025
Betting Odds: Jaguars +145, 49ers -174

The Jaguars Can Win If…

The Jacksonville Jaguars secured a 17-10 win against the Houston Texans in their most recent game. Trevor Lawrence threw for 222 yards, though he had one interception. Travis Etienne Jr. was a key player, rushing for 56 yards and scoring a touchdown.

The Jaguars have shown strong rushing abilities, with Travis Etienne Jr. ranking 3rd in the league for rushing yards. Their defense has been effective, recovering fumbles and intercepting passes. These strengths can help them win their next game.

Trevor Lawrence is projected to throw for over 225 yards in the upcoming game. With support from players like Brenton Strange and Brian Thomas Jr., the Jaguars have the potential to score effectively. Their defense, led by Tyson Campbell and Travon Walker, can stop the opponent’s offense.

The 49ers Can Win If…

The San Francisco 49ers are coming off a narrow 16-15 win against the Arizona Cardinals. Mac Jones led the charge with 284 passing yards and a touchdown. Christian McCaffrey contributed with 52 rushing yards and 10 receptions, showcasing his versatility on the field.

The 49ers have shown strong performances in their passing game, ranking 4th in the league last season with 4,234 passing yards. Their defense has also been effective, ranking 8th in opponent offensive yards allowed. These stats highlight their balanced approach on both sides of the ball.

Key players like Ricky Pearsall and Fred Warner are expected to make significant impacts. Pearsall has been a top target, with 281 receiving yards in three games. Warner, with his defensive prowess, consistently disrupts opposing offenses, making the 49ers a formidable opponent in any game.

The Lean

For the spread pick, the recommendation is to take the 49ers at -3.0. The 49ers have been strong as favorites, going 6-3 against the spread in their last nine games. The Jaguars have struggled as underdogs, with a 2-4 record against the spread in their last six games. The model projects a score of 49ers 27, Jaguars 21.

For the over/under pick, the recommendation is to go with the over at 47.0. The 49ers have hit the over in four of their last six games. The Jaguars have also seen high-scoring games, with four straight overs after a win. The model projects a total score of 48 points, just over the line.

Jaguars vs 49ers Preview

The San Francisco 49ers (3-0) will try to stay unbeaten despite major injuries when they host the Jacksonville Jaguars (2-1) on Sunday. Brock Purdy (toe/shoulder) and Mac Jones (knee) are both limited in practice, raising the possibility that Adrian Martinez could make his first NFL start.

San Francisco’s passing attack is further compromised with George Kittle and multiple wideouts sidelined. Defensively, losing Nick Bosa to a season-ending knee injury forces rookies and depth players to step up.

Jacksonville arrives off a 17-10 win over Houston, powered by a defense tied for fifth in scoring and first in forced turnovers. Rookie Travis Hunter continues his rare two-way role, contributing on both offense and defense while being eased into defined positions.

Injury Report

The 49ers’ injury list is long: Purdy, Jones, receivers Ricky Pearsall, Jauan Jennings, and Jordan Watkins all limited or sidelined. Yetur Gross-Matos (knee) and C.J. West (thumb) did not practice, while Renardo Green, Deommodore Lenoir, Connor Colby, and Kalia Davis were limited.

For Jacksonville, Dyami Brown (shoulder) did not practice. Bhayshul Tuten (shoulder) and linemen Ezra Cleveland (ankle), Patrick Mekari (elbow), and Wyatt Milum (knee) were limited.

Betting Results and Trends

The 49ers opened as home favorites on the NFL odds page, but the line has tightened with QB uncertainty and Bosa’s absence. San Francisco is 2-1 ATS, fueled by defense, with two Unders. Jacksonville is also 2-1 ATS, leaning Under with a defense allowing just 17 points per game. Turnovers may decide the cover.

What It Means Moving Forward

If San Francisco finds a way to win short-handed, it reinforces their depth as NFC contenders. Jacksonville has never beaten the 49ers in California, but their defensive surge and Hunter’s versatility give them a chance at a statement win.

ScoresAndStats Handicappers and Picks

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San Francisco 49ers vs Jacksonville Jaguars Picks and Predictions September 28th 2025