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Jacksonville Jaguars @ San Francisco 49ers Week 4 Best Bets

todaySeptember 26, 2025

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By John O’Leary

 

The now 2-1 Jacksonville Jaguars travel out west to face the 3-0 San Francisco 49ers. The 49ers are a team that, despite being mauled by various injuries through the first three games, has found a way to win in every contest. The Jaguars have remained relatively healthy through the first three weeks, with the only major notes being their two wide receivers, Brian Thomas Jr (wrist) and Dyami Brown (shoulder). The 49ers, on the other hand, have not been so lucky. Quarterback Brock Purdy has missed two games after suffering a shoulder injury in Week 1, tight end George Kittle was placed on short-term IR with a hamstring strain, defensive end Nick Bosa underwent ACL repair surgery earlier this week, and both wide receivers Ricky Pearsall and Jauan Jennings have found themselves on the 49ers injury report during the week. Simply put, the 49ers are banged up across almost every position group, and the Jaguars have found a way to remain reasonably healthy through three weeks.

 

Best Bet: Under 46.5 Game Total -110

The Jaguars and 49ers both come into this game with defenses playing very well. Pro Football Focus has the Jaguars ranked as the second best defense and the 49ers as the fifth best. The Jaguars and 49ers are a combined 2-4 against this total hitting the over, and with two defenses playing extremely well the under gains even more playability. The 49ers are coming into this contest averaging just over 19 points a game with the Jaguars averaging just over 23 points per game.

Pair this with the 49ers injury issue surrounding their offense, and the under looks like a quality play on Sunday.

I consider this a 2 unit play on Sunday but would wait to play it before game time to see if the total in this game does continue to go up.

 

Player Prop: Brenton Strange Anytime TD +300

Strange has been a consistent safety valve for Trevor Lawrence through the first three weeks, hitting three or more receptions in all three contests along with averaging just over 45 yards a game this season. Strange will also be facing a 49ers defense that has allowed a touchdown to tight ends in their previous two games. This matchup against the 49ers seems to be a prime opportunity for Strange to get his first red zone target, as he has been one of the only reliable sets of hands for this Jaguars passing attack.

I consider this a half unit play.

 

You can email John at [email protected] or find him on X at @JohnOleary22

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todaySeptember 26, 2025