Fresh off a grind-it-out win over the Houston Texans, the Jacksonville Jaguars (2-1) are preparing for a tilt Sunday against the San Francisco 49ers (3-0) in Northern California.
The Niners are one of the wonders of this young, NFL season. Yes, their schedule has not been a juggernaut. That said, they are figuring things out despite not having their starting quarterback, Brock Purdy, and top wide receivers, Jauan Jennings, and Brandon Aiyuk. Sunday, San Francisco eked out a 16-15 win over the Arizona Cardinals. Mac Jones is now 2-0 as the replacement for Purdy. The injury bug struck again, though, Sunday as Nick Bosa tore his ACL and is out for the season. If somehow the 49ers keep winning, watch Fred Warner’s stock for Defensive Player of the Year rise.
Liam Cohen was hired to fix Trevor Lawrence and lead the Jaguars to better days. Not sure yet about the former but the latter may be happening as Jacksonville knocked off Houston, 17-10, on Sunday. Jacksonville’s defense limited C.J. Stroud and the Texans to 13 first downs, one trip inside the Red Zone, and 271 total yards. The Jags have won two of their first three games for the first time since 2022.
Lets take a deeper dive into this Week 4 matchup between the Jaguars and the 49ers and find a couple of sweats.
NBC Sports has all the latest info and analysis you need, including how to tune in for kickoff, odds from DraftKings, player news and updates, and of course our predictions and best bets for the game from our staff of experts.
Game Details and How to watch the Jaguars at the 49ers live Sunday
- Date: Sunday, September 28, 2025
- Time: 4:05PM EST
- Site: Levi’s Stadium
- City: Santa Clara, CA
- Network/Streaming: FOX
Want to check out the other games on the NFL schedule this week? We’ve got you covered right here on NBC Sports with all the matchup, venue, game-time and TV/streaming info so you won’t miss any of the action!
Game odds for the Jaguars at the 49ers
The latest odds as of Wednesday courtesy of DraftKings:
- Moneyline: Jacksonville Jaguars (+140), San Francisco 49ers (-166)
- Spread: 49ers -3
- Total: 47.5 points
This game opened at 49ers -3.0 with the Game Total set at 45.0.
Be sure to check out DraftKings for all the latest game odds & player props for every matchup this week on the NFL schedule!
Quarterback Matchup for Jacksonville at San Francisco
- Jaguars Expected Starting QB: Trevor Lawrence
Last Game: 9/21 vs. Houston – 20-40 (50%), 222yds, 0 TDs, 1 INT, Sacked 2 times, 2 carries for 9yds
Season: 3GP, 63-113 (55.8%), 671yds, 4 TDs, 4 INTs, Sacked 3 times, 8 carries for 25yds - 49ers Expected Starting QB: Mac Jones
Last Game: 9/21 vs. Arizona – 27-41 (65.9%), 284yds, 1 TD, 1 INT, Sacked 1 time, 1 carry for -1yds
Season: 2GP, 53-80 (66.3%), 563yds, 4 TDs, 1 INT, Sacked 4 times, 7 carries for 5yds
Jaguars at 49ers team stats, betting trends
- The 49ers have won 4 straight games against the Jaguars
- The 49ers are 2-8 against the spread in their last 10 games
- The 49ers’ last 3 games have gone OVER the Total
Jaguars Player Injuries
- WR Dyami Brown (shoulder) is listed as questionable for Sunday’s game
- Backup LG Wyatt Milum (undisclosed) is listed as questionable for Sunday’s game
49ers Player Injuries
- QB Brock Purdy (toe) is listed as questionable for Sunday’s game
- DE Nick Bosa (knee) has been declared out for the season due to an ACL injury
- WR Jauan Jennings (shoulder/ankle) is listed as questionable for Sunday’s game
- QB Mac Jones (knee) is listed as questionable for Sunday’s game
- OT Spencer Burford (knee) was placed on IR Saturday and is OUT for this Sunday’s game
- DE Mykel Williams (wrist) is listed as questionable for Sunday’s game
- CB Renardo Green (neck) is listed as questionable for Sunday’s game
- DT CJ West (thumb) is listed as questionable for Sunday’s game
Rotoworld Bet Best Bets
Please bet responsibly. If you or someone you know has a gambling problem, call the National Gambling Helpline at 1-800-522-4700.
Our model calculates projections around each moneyline, spread and over/under bet for every game on the NFL calendar based on data points like past performance, player matchups, stadium information and weather forecasts.
Once the model is finished running, we put its projection next to the latest betting lines for the game to arrive at a relative confidence level for each wager.
Best bets our model is projecting for this week’s game between the Jaguars and the 49ers:
- Moneyline: NBC Sports Bet is staying away from a play on the Moneyline.
- Spread: NBC Sports Bet is leaning towards a play ATS on the San Francisco 49ers at -3.5.
- Total: NBC Sports Bet is recommending a play on the under on the Game Total of 47.5.
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