The San Francisco 49ers have only played one game of the 2025 NFL season, and already they are dealing with significant injury issues.
San Francisco’s dramatic 17-13 win over the Seattle Seahawks was a pyrrhic one, as tight end George Kittle suffered a hamstring injury that will see him miss four weeks after he was placed on injured reserve.
Losing Kittle was a massive blow on its own, but worse news has come this week concerning quarterback Brock Purdy, who is reportedly set to miss two to five weeks with turf toe, a sprain at the base of the ligaments of the big toe.
The 49ers are now set to turn to backup Mac Jones in Week 2, with the date of Purdy’s return critical as San Francisco aims to avoid falling into a hole that quickly diminish hopes of returning to the playoffs.
Jones is a quarterback whom many see as a perfect fit for head coach Kyle Shanahan’s offensive system. The 49ers had the chance to select him third overall in the 2021 draft, but instead went with Trey Lance in a significant misstep, with San Francisco’s blushes spared by the emergence of seventh-round pick Purdy.
Over four years on, Jones is now set to get his chance to play for Shanahan in a regular-season game, but there’s no doubt he will be a downgrade from Purdy, making a potential five-game absence a huge challenge for San Francisco to overcome.
Here’s a look at the games Purdy could miss.
Week 2: @ New Orleans Saints
Purdy is set to be a spectator for the most manageable game of the stretch, with the 49ers visiting a Saints team many view as the favorites for the number one overall pick in next year’s draft.
The Superdome is an imposing and very loud arena, and the Saints hung tough against the Arizona Cardinals last week, only losing 20-13.
Still, the 49ers will likely be confident of their defense carrying the load against quarterback Spencer Rattler and moving to 2-0. With the games that follow, there’s an argument to be made that, if Purdy is out for a full five weeks, their success in avoiding an upset in this one could make or break the 49ers’ season.
Week 3: vs. Arizona Cardinals
This is where things start to get tougher.
The Cardinals are by no means a juggernaut, but they are a team on the rise and won this same fixture last season thanks to a fourth-quarter comeback.
Kyler Murray is a quarterback from whom his undoubtedly lofty ceiling always seems just out of reach, but he has consistently confounded the 49ers with his dual-threat ability. On the other side of the ball, the Cardinals have the defensive talent to make it a long afternoon for Mac Jones if Purdy does indeed miss San Francisco’s home opener at Levi’s Stadium.
Week 4: vs. Jacksonville Jaguars
Should Purdy return for this matchup, the 49ers will be expected to prevail.
The 49ers have dominated recent games with the Jaguars, most recently crushing them on the road en route to an appearance in Super Bowl 58 in the 2023 season.
But a Purdy absence would make a meeting with Trevor Lawrence, for whom Jones served as the backup last year, substantially more difficult.
The Jags have a sharp offensive mind at head coach in Liam Coen who is hoping to elicit elite level quarterback play from former number one pick Lawrence, and are blessed with significant young talent on the offensive side of the ball.
There’s also the revenge game narrative at play here, with former San Francisco defensive tackle Arik Armstead aiming to make the 49ers pay for parting company with him last year following a contract dispute.
Week 5: at Los Angeles Rams
After the Jaguars game, the 49ers face a short week as they make the trip south to face their in-state rivals on Thursday Night Football.
It has become the norm for 49ers fans to pack out SoFi Stadium for this game, with the home of the Rams coming to be known as ‘Levi’s South’ by San Francisco fans.
But the 49ers saw their dominance of this rivalry interrupted last season as the Rams swept the series, winning at home with a dramatic fourth-quarter comeback. If Purdy is still unavailable, then it will be very difficult to see the Niners prevailing in what will be Kittle’s last game on the sidelines.
Week 6: at Tampa Bay Buccaneers
The benefit of playing on a short week is the extended rest ahead of the subsequent game, and the 49ers will be hoping that plays a role in them recording another win in Tampa, having come through a thriller against Baker Mayfield and Co. last season.
Tampa Bay, though, has a loaded offense and a defense boasting talent at every level. The cross-country trip would be extremely tough even with Purdy back in the fray. Facing the Bucs on the road with Jones at quarterback would be a recipe for a miserable trip.
