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Jacksonville Jaguars at San Francisco 49ers Preview & Picks – Niners To Remain Unbeaten In NFL

leigh-copson
24 Sep 2025
leigh-copson
Leigh Copson 24 Sep 2025
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  • Jacksonville Jaguars at San Francisco 49ers picks for Sunday, September 28
  • Game is taking place at Levi's Stadium
  • Preview, predictions, stats & form
(Getty Images)
    Jacksonville Jaguars at San Francisco 49ers Preview & Picks
  • Jacksonville Jaguars at San Francisco 49ers Preview & Picks
  • Head To Head
  • Jacksonville Jaguars Form
  • San Francisco 49ers Form

Jacksonville Jaguars at San Francisco 49ers Preview & Picks

San Francisco are tipped to cover as they maintain their perfect record.

Brock Purdy’s return is a big boost for the 49ers, but we still expect them to lean on Christian McCaffrey and a defense that is still a solid unit despite the loss of Nick Bosa.

  • San Francisco 49ers are 3-0 this season
  • Jacksonville Jaguars are 1-12 in their last 13 road games
  • The Under has cashed in 2 of Jacksonville’s first 3 games
  • The Under has hit in 2 of San Francisco’s first 3 games

Head To Head

  • San Francisco 49ers lead the all-time series 5-2
  • San Francisco 49ers won 34-3 when the two teams last met in November 2023

Jacksonville Jaguars Form

Jacksonville make the long trip to the West Coast looking to back up their second win of the season.

The Jaguars made a change at head coach in the offseason, bringing in Liam Coen, and it has so far been a decision that has paid off for the franchise.

They opened up the season with a home game against Carolina and ran out 26-10 winners.

Jacksonville were unable to follow that up on the road a week later as they travelled to Cincinnati for a 31-27 defeat to the Bengals, but they did rebound immediate.

The Jaguars returned home last weekend and register an important 17-10 victory over division rivals Houston to improve to 2-1.

San Francisco 49ers Form

San Francisco enter this matchup boasting a 100% record, having won each of the first three games of the season.

The 49ers appeared to suffer from a post-Super Bowl hangover as they missed out on the playoffs last season, but they have made a solid start to their quest for a return to the postseason in 2025.

They kicked off the season with back-to-back road games, and came away from both of them with a victory.

San Francisco opened with a 17-13 victory in Seattle, and backed that up a week later as they travelled to New Orleans to beat the Saints 26-21.

The 49ers then made it three wins in a row in their home opener, as they snatched a 16-15 victory over NFC West rivals Arizona last weekend.

Verdict

There is no doubting that this Jacksonville team looks much improved under Liam Coen.

However, this is a long trip to face a good San Francisco team, so we are leaning towards the 49ers delivering a win and cover.

Best Bet1: San Francisco -3.5 Spread @-111.11 at Stake.us - 4 Units
Best Bet2: Under 46.5 Total Points @-111.11 at Stake.us - 2 Units
San Francisco -3.5
Spread
@-111.11 - 4 Units
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Bet at Stake.us
Under 46.5
Total Points
@-111.11 - 2 Units
55 Stake Cash no deposit & 550,000 Gold Coins & 5% Rakeback
Use promo code NEWBONUS

Sign up with the code NEWBONUS. When you verify your account get 25 Stake Cash for free PLUS 250,000 Gold Coins and 5% Rakeback! No deposit required. Login each day for the next 30 days and get an additional 30 Stake Cash AND 300,000 Gold Coins. 21+ only. T&Cs apply. Excludes WA, NY, NV, ID, KY, MI, VT, NJ, DE, WV, PA, RI & MD.

Bet at Stake.us