The Jacksonville Jaguars got a crucial divisional win in Week 3, downing the Houston Texans 17-10 to move to 2-1 on the 2025 NFL season. They're within arm's reach of the top of the AFC South, just behind the undefeated Indianapolis Colts. With the Colts set to take on a bona fide contender in the Los Angeles Rams in their next game, the Jaguars could make some major headway if they're able to take care of business against the San Francisco 49ers.
Of course, Jacksonville is also taking on a prospective title team. The injury report leans heavily in the Jaguars' favor, with the Niners losing EDGE Nick Bosa for the season and just bringing back quarterback Brock Purdy from an accelerated turf toe recovery due to Mac Jones going down with a PCL sprain.
Still, San Francisco has more than enough talent to win even without Nick Bosa, not just in Week 4 but throughout the rest of the season. Jacksonville faces a steep climb trying to get its first road victory this season against a proven playoff team after a five-hour flight with a three-hour time delay.
The Jacksonville Jaguars are coming into their clash with the San Francisco 49ers as significant underdogs. This is both a testament to the Niners' encouraging undefeated start to the 2025 NFL season and a reflection of the doubt still surrounding the Jaguars.
Jacksonville could easily be undefeated if a few plays had swung its way in Week 2 versus the Cincinnati Bengals. However, they also squeaked by the Houston Texans in their last game, requiring three takeaways from the defense in order to eke out a 17-10 win.
From my count, the #Jaguars are 8-20 all-time when traveling to play on the West Coast.
— Daniel Griffis (@DanDGriffis) September 25, 2025
1-5 vs Chargers
3-4 vs Raiders
3-3 vs Broncos
0-4 vs Seahawks
1-1 vs Cardinals
0-2 vs Niners
0-1 vs Rams (St Louis excluded)
8-20
Needless to say, the Jaguars' history of incompetence is still being counted against them heading into Week 4. Four out of five editors on NFL.com's panel picked the 49ers in this one, giving them an average margin of victory of 5.5 points. Brooke Cersosimo predicted that San Francisco would take it, 23-18:
"There are bigger questions around the Jaguars, a talented jamboree that has yet to get everyone on the same page in the same game. The defense has set the tone for this team so far, ranking first in the NFL in takeaways (nine), fifth in points allowed and 10th in yards. The offense, on the other hand, has been far too inconsistent. Trevor Lawrence hasn't cleaned up his turnovers and has struggled in the second half of games this season, posting a 56.1 passer rating and completing just 50 percent of his passes in the third and fourth quarters (both worst in the NFL)."
"Brian Thomas Jr. has caught just 28 percent of his 25 targets, and Travis Hunter has underwhelmed -- though head coach Liam Coen told reporters they are working to put the rookie in better positions to become more productive on Sundays. Right now, in terms of the overall health of these teams, the ceiling might be higher for Jacksonville, but can it avoid costly mistakes? It's hard to say yes at this point in time."
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