TAMPA, Fla. — Since entering the league in 2018, San Francisco 49ers linebacker Fred Warner has missed only one game out of a possible 122 because of injury.

Which is why, when Warner departed Sunday’s 30-19 loss to the Tampa Bay Buccaneers because of a broken and dislocated right ankle in the first quarter, his teammates were in disbelief.

Warner’s injury will require season-ending surgery, 49ers coach Kyle Shanahan said after the game.

“He’s one of our best players, also a huge leader, so obviously, a huge blow,” Shanahan said. “I feel bad for Fred right now.”

Warner suffered the devastating injury with just under eight minutes left in the opening quarter. On first-and-10 at Tampa Bay’s 36, running back Rachaad White ran off left tackle for a gain of 10 yards. As Warner attempted to corral White, who cut inside him, Niners safety Ji’Ayir Brown brought White down and Brown’s legs rolled into the back of Warner’s ankle.

Brown reacted quickly, knowing that Warner might be seriously hurt, and teammates quickly put their hands on their heads and dropped to a knee as they watched San Francisco’s medical staff surround Warner.

After the game, Brown was emotional, describing the loss of Warner, a player he said has been like a “big brother” to him.

“I was right there when it happened,” Brown said. “Seeing him go down, a guy that doesn’t go down, you know what I mean? It’s draining. I think it kind of drained the stadium. Everybody felt that.”

A couple of minutes after Warner’s injury, Niners medical and training staff placed his right foot and ankle in an air cast, and he was taken to the locker room on a cart. Before he departed, Niners players wished him well as the seriousness of the injury seemed to hit them.

Wide receiver Jauan Jennings said he had to take some nausea medicine because he was “sick to his stomach” watching Warner leave with the injury while others noted the shock at seeing a player, who has made a career of being available, in such condition.

“It’s heartbreaking,” left tackle Trent Williams said. “Fred, not only is he one of the best linebackers to ever play the game, but he is the heart and soul of this team, not just the heart and soul of this defense. It’s one thing to see somebody go down and go to the blue tent, and nobody really knows what’s going on. When you see a guy that’s injured like that, it’s really like a gut punch. It’s really hard to continue the intensity and playing that game like that never happened.”

With Warner in the locker room, the 49ers turned to second-year linebacker Tatum Bethune to play middle linebacker, though weakside linebacker Dee Winters handled communication with defensive coordinator Robert Saleh.

Although the 49ers gave up touchdown drives to the Bucs on three of their first four full possessions after Warner’s departure, Bethune led the team in tackles with 10. Shanahan indicated after the game that Bethune will get the first opportunity to replace Warner for the rest of the season.

Bethune, who was a seventh-round pick in the 2024 draft, has one NFL start, the 2024 season finale in Arizona, in which he had three tackles on 39 defensive snaps.

“You prepare as a starter for reasons like this,” Bethune said. “Fred getting hurt was unfortunate, but this is why we are all professionals and we’ve all got a job to do.”

Even as Warner was taken to the locker room on the cart, teammates said he was going out of his way to encourage them to try to beat the Bucs. Warner stayed in Raymond James Stadium for the entire game, and Shanahan had him address the team in the locker room when the game was over.

Warner’s message: There’s a lot of football left and a lot of things the Niners can accomplish, even without him.

“It’s obviously tough losing him and he’s our brother and it sucks, but we have got a lot of football left,” linebacker Luke Gifford said. “And we’ve got the tools to win games.”

Warner’s injury wasn’t felt just in the Niners’ locker room. Buccaneers quarterback Baker Mayfield opened his postgame news conference by sending thoughts and prayers to Warner. Tampa Bay coach Todd Bowles echoed that sentiment.

“It was sickening,” Bowles said. “He’s one of the best players in the league. A great guy on top of that. You hate to see something like that happen. Hopefully, he has a speedy recovery. That kind of breaks your heart, no matter what side of the ball you’re on.”

Warner has been the leader of San Francisco’s defense since his arrival in 2018 and was positioned to break Hall of Fame linebacker Patrick Willis’ franchise record for tackles in a career Sunday before the injury. Warner needed five tackles to reach that mark and had one at the time of the injury.

For the Niners, picking up the pieces after Warner’s injury will be more difficult because the defense is dealing with other significant injuries. The 49ers lost star defensive end Nick Bosa to a torn ACL in his right knee in Week 3, and he, too, is out for the season.

The 49ers will play the final 11 games of the year without their two best and most indispensable defenders while also playing chunks or all of the season without tight end George Kittle (hamstring), quarterback Brock Purdy (toe), receivers Ricky Pearsall (knee), Brandon Aiyuk (knee) and Jennings (ankle, ribs, shoulder).

Jennings revealed after the game that the injuries that have limited him this season have mounted in more ways than previously known. He said he played Sunday with five broken ribs, a shoulder he estimated at about 20 percent healthy, and has had both high and low ankle sprains.

“Everyone knows it’s difficult when you lose your better players and your leaders,” Shanahan said. “It’s tough. It’s huge with Nick, obviously huge with Fred. Hopefully, we’ll get Kittle back here and some of the other guys, but that’s going to give opportunities to other guys. These are the moments guys got to step it up. I’m glad that we played some decent football to put us in this position, at least with the record, and we’ve got to find a way to get better everywhere else throughout this year.”