Jacksonville Jaguars vs. San Francisco 49ers Picks and Prediction for Sunday, September 28, 2025
Use Code SSWC The Jacksonville Jaguars (2-1) are looking to build off their 17-10 home win on Sunday against the Houston Texans in Week 3. Quarterback Trevor Lawrence struggled in the game as he completed 20-of-40 passes for 222 yards with zero passing touchdowns and one interception.
The San Francisco 49ers (3-0) are looking to build upon their 16-15 home win on Sunday over the Arizona Cardinals. Quarterback Mac Jones was able to step up as he completed 27-of-41 passes for 284 yards with a passing touchdown and an interception. Four quarters, one clear read — NFL picks for Jacksonville Jaguars vs. San Francisco 49ers.
Jaguars Looking to Improve
The Jacksonville Jaguars are coming off a 17-10 home win in Week 3 against the Houston Texans. Quarterback Trevor Lawrence struggled a bit, but the offense was able to do enough to win, with the running game averaging 3.6 yards per carry and two touchdowns.
The defense of the Jaguars stepped up as they allowed the Houston Texans to record 10 points on 271 total yards (184 passing, 87 rushing). The defense stepped up and forced three turnovers (one fumble, two interceptions) on the day to win. Rookie CB/WR Trais Hunter is playing more on both sides. He played at least 37 snaps on both offense and defense in the last two weeks. He has 10 catches for 76 yards and nine tackles with one pass breakup on defense.
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The Jacksonville Jaguars are stepping up offensively so far this season as they’re scoring 23.3 points per game. The defense is leading the way with 17.0 points per game against. They allow just 292 yards per game overall (10th) and 82.7 rushing yards per game (4th). On offense, they rank 6th with 141.7 rushing yards as Travis Etienne leads the way with 270 yards on the ground.
Injury Report for Jacksonville
- Running back Bhayshul Tuten: Shoulder (Questionable)
- Offensive guard Ezra Cleveland: Ankle (Questionable)
- Offensive tackle Patrick Mekari: Elbow (Questionable)
- Offensive tackle Wyatt Milum: Knee (Questionable)
- Wide receiver Dyami Brown: Shoulder (Questionable)
- Offensive tackle Cooper Hodges: Knee (OUT)
- Linebacker Jalen McLeod: Lower Body (OUT)
- Cornerback Caleb Ransaw: Lower Body (OUT)
49ers Looking to Step Up This Season
The San Francisco 49ers were able to secure a 16-15 home win in Week 3 against the Arizona Cardinals on Sunday. The offense was able to score just 16 points on 355 total yards (282 passing, 73 rushing). Quarterback Mac Jones had a good showing, as we highlighted earlier. Running back Christian McCaffrey led the rushing stats as he had 17 rushes for 52 yards (3.1 yards per carry) while also adding 10 grabs for 88 yards (8.8 yards per reception), but could not find the end zone. The one major issue was the fact that they were 2-for-10 on third down.
The defense of the 49ers stepped up as they allowed 15 points on 260 total yards (154 passing, 106 rushing). San Fran was able to run the football well against them as they averaged 3.8 yards per attempt. However, the Dolphins couldn’t keep drives alive as the 49ers allowed just 16 total first downs. San Francisco was quiet defensively as they had just one sack and zero takeaways while losing their best defensive player for the season.
At quarterback, Mac Jones (knee) was limited in practice and Brock Purdy (left shoulder/toe) has missed two straight games. The third-string QB is Adrian Martinez, who can run extremely well, but has yet to see action in an NFL game.
The 49ers have been a struggling offensive team right now as they are putting up 19.7 points per game. However, the defense has been stellar as they are allowing 16.3 points per game.
Injury Report for San Francisco
- Cornerback Deommodore Lenoir: Illness (Questionable)
- Defensive end Yetur Gross-Matos: Knee (Questionable)
- Wide receiver Ricky Pearsall: Knee (Questionable)
- Offensive guard Connor Colby: Groin (Questionable)
- Defensive end Nick Boss: Knee (OUT)
- Quarterback Brock Purdy: Toe (Questionable)
- Wide receiver Jordan Watkins: Calf (Questionable)
- Cornerback Renardo Green: Neck (Questionable)
- Defensive tackle CJ West: Thumb (Questionable)
- Wide receiver Juwan Jennings: Ankle (Questionable)
- Quarterback Mac Jones: Knee (Questionable)
- Offensive tackle Spencer Burford: Ankle (OUT)
- Offensive tackle Ben Bartch: Ankle (OUT)
- Tight end George Kittle: Hamstring (OUT)
- Wide receiver Jacob Cowing: Hamstring (OUT)
- Cornerback Jakob Robinson: Forearm (OUT)
- Safety Malik Mustapha: Knee (OUT)
- Defensive tackle Kevin Givens: Pectoral (OUT)
- Quarterback Kurtis Rourke: Knee (OUT)
- Wide red Brandon Ajyuk: Knee (OUT)
Jacksonville Jaguars vs. San Francisco 49ers Pick
Spread Pick for Jaguars vs. 49ers
- Jacksonville Jaguars +3.5 (4 units)
The 49ers are just too banged up to believe they can keep continuing to play close games and win. Both quarterbacks have now found their way on the injury report. The Jaguars are averaging 5.1 yards per rushing attempt throughout the season, so they are going to be able to dominate the trenches and keep getting first downs. They stop the run, so McCaffrey will be limited in this game. Take the Jacksonville Jaguars to cover the spread in this game here.
Over/Under Pick for Jaguars vs. 49ers
- UNDER 47.5 (4 units)
The San Francisco 49ers have been leaning on running back Christian McCaffrey, but he has not been able to step up and find a significant amount of yards as he is averaging 3.4 yards per rushing attempt, which is tied for 118th. The injuries to TE George Kittle and WR Brandon Aiyuk have really limited the offense. Trevor Lawrence has been unable to get going with only four passing touchdowns in the first three games, while also turning over the ball with four interceptions. Both defenses have also been stepping up and should be able to force punts throughout the game. All in all, go with UNDER 47.5 POINTS in this game.
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