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For the first five weeks of the 2025 season, the 49ers survived devastating injuries and pulled off a series of last-minute high-wire acts to seal four wins that lifted the team to the top of the NFC West. 

When linebacker Fred Warner was carted off the field with an aircast on his ankle on Sunday in Tampa, everything changed.

The 49ers superstar has been the most dependable player of the Kyle Shanahan era, and a crushing injury that could keep him out for an extended period of time and potentially the remainder of the regular season threatens to derail the team’s progress.

Warner’s loss had – and will continue to have – a catastrophic impact on the 49ers’ defense as the unit made multiple backbreaking assignment errors on Bucs touchdowns in a 30-19 defeat.

The linebacker was injured on the Bucs’ second drive of the game, when 49ers safety Ji’Ayir Brown rolled up on Warner’s ankle, which bent at an angle that CBS’ broadcast crew deemed too gruesome to show close up or in slow motion.

Late special teams miscues from Tampa Bay including a missed field goal attempt and a roughing the punter penalty left Mac Jones and the San Francisco offense with opportunities to claw back, but the 49ers committed too many of their own mistakes to make up for a defense that was rudderless without its best player.

With under a minute to go in the second quarter, Bucs quarterback Baker Mayfield sent Kameron Johnson in motion from left to right across the formation and the 49ers’ defense completely lost track of him. No one covered Johnson at the snap, leaving him wide open for a 34-yard touchdown reception on his first target of the season.

Late in the third quarter, rookie safety Marques Sigle was too slow to rotate over and cover Tez Johnson, who had a free release up the seam and made an acrobatic snag to haul in a 45-yard toss from Mayfield at the front of the end zone. 

Tez Johnson’s touchdown was particularly crushing for the 49ers as it came in the wake of an MVP moment for Mayfield. On 3rd and 14 at the Bucs’ 41-yard line, Bryce Huff and Trevis Gipson collapsed the pocket and had Mayfield in their grasp, but the quarterback wiggled out of their reach and then eluded a handful of 49ers’ defenders before extending the ball beyond the first down marker for a 15-yard gain. 

A 49ers defense that should have forced a Bucs punt instead watched Tez Johnson race open two plays later to extend Tampa Bay’s lead to eight points. 

The touchdowns, keyed by blown coverages, exposed the reality of the depth issues that could continue to plague the 49ers for the remainder of a season that began in such promising fashion.

Tampa Bay also entered Sunday’s game with four one-score wins, and the Bucs’ offense was dealing with its own significant injury issues. After veteran wide receivers Mike Evans and Chris Godwin were ruled out earlier in the week, the Bucs lost star rookie Emeka Egbuka, who entered the matchup with 25 receptions and five touchdowns, to a hamstring injury. 

Without Warner and star pass-rusher Nick Bosa, the 49ers’ defense lacks elite closing speed in its front seven and is missing the two players most likely to generate turnovers. Without quarterback Brock Purdy, tight end George Kittle, and wide receivers Ricky Pearsall and Brandon Aiyuk, the 49ers’ offense is missing steady presences and game-changing explosiveness required to survive the rigors of a 17-game season.

Jones has filled in admirably for Purdy, throwing for 300-plus yards in back-to-back games, but his first-quarter interception on a pass intended for Kendrick Bourne put the 49ers in an early hole. On San Francisco’s first possession, Bourne broke in toward the middle of the field when Jones delivered a pass outside the numbers that was intercepted by Kindle Vildor, who tripped twice but still set the Bucs up for a two-play, 12-yard touchdown drive. 

Jones’ second interception, which came on 4th and 6 with less than six minutes on the clock, essentially killed the 49ers’ chances of a miracle comeback. Jamel Dean’s pick was made possible by back-to-back mistakes from the 49ers’ offensive line, which couldn’t generate a push on Jones’ QB sneak attempt on 3rd down and 1. As Jones walked up to the line of scrimmage on 4th down, right guard Dominick Puni committed a false start penalty, taking a run play out of the equation. 

As reporter David Lombardi gathers reaction from the 49ers’ locker room, here are our early takeaways.

Football is a sport of injuries. But seeing Warner — who had been taking such immense joy in the 49ers’ white-knuckle victories to begin this season — go down has to be the most painful gut punch that Shanahan’s team has taken to date.

Why?

Because Warner is a true ironman. People might expect injuries to this beaten-up 49ers roster, but they don’t expect one to fell Warner. Including Sunday, Warner has played in 132 of 133 possible NFL games over his eight-year career. Seeing that cart come out for what’s being reported as a dislocated ankle was downright jarring for the 49ers.

And yes, the impact was evident. Credit the 49ers for stiffening up on the drive immediately following Warner’s exit. But it turned into a bloodbath after that. Tampa Bay averaged a staggering 10.2 yards per play over three straight explosive touchdown drives, including the inexcusable missed sack on Mayfield that led to a Bucs score.

Following Warner’s exit, the 49ers defense was lost.

Where do the 49ers go from here? Well, it appears that their only path to contention now lies in extreme offensive ball control to shield this decimated and relatively inexperienced defense from exposure. Defensive coordinator Robert Saleh will get as creative as he can, but the pressure for elite 49ers’ offensive production is on.

And the only path to that likely lies in the returns of Purdy and Kittle.

Make no mistake: Even with the two interceptions (the first of which might not have been his fault), that was another eminently gutsy performance from Jones, who was in too much pain to throw over much of the practice week. He muscled up to throw for 347 yards on Sunday, threading a handful of excellent passes to all corners of the field.

But Jones is not a mobile quarterback. There’s a reason he’s the 49ers’ backup. He’s certainly not spinning out of sacks like Mayfield did. And yes, Brock Purdy has engaged in some of that escapism over his career — and the 49ers certainly missed it on Sunday.

Tampa Bay coach Todd Bowles, as expected, blitzed Jones relentlessly. The Bucs racked up six sacks against an already-injured QB. With the 49ers’ defense bleeding yardage on the other end, forcing Jones to pass, Shanahan’s offense became a sitting duck.

Again, the 49ers need Purdy and Kittle back now — more than ever.