SANTA CLARA, Calif. — The San Francisco 49ers will likely be without three of their top offensive players and possibly two of their top defensive players on Sunday against the Los Angeles Rams.

After missing practice Thursday and Friday, tight end George Kittle (hamstring) has been listed as questionable for Sunday. If Kittle does not play against the Rams, he would join running back Christian McCaffrey (calf/Achilles tendinitis) and wide receiver Deebo Samuel (calf) as key offensive options who have been ruled out.

On the other side of the ball, defensive end Nick Bosa and cornerback Charvarius Ward, two of the Niners’ top defenders, are considered questionable. Coach Kyle Shanahan said Bosa suffered a rib injury during a one-on-one period on Thursday and was limited in that practice and again on Friday. Ward also missed Thursday’s practice with hamstring and knee soreness, but he participated in a limited amount of practice on Friday.

Kittle and Ward were surprisingly added to the injury report on Thursday after training fully on Wednesday.

“(Kittle) and Charvarius, they were stiff after practice (Wednesday), like a lot of guys,” Shanahan said. “They came in Thursday morning and they were still stiff. And still today with Kittle. That’s the severity of it.”

In better injury news for the Niners, safety Talanoa Hufanga has been cleared to return after recovering from a torn ACL in his right knee. Hufanga was listed as questionable the first two weeks as he worked his way back into the mix, but has no designation against the Rams and is good to go.

Shanahan said Hufanga is ready for the game, and how much he plays will depend on how things go series by series. That means George Odum and Malik Mustapha could get some work opposite Ji’Ayir Brown at safety.

Nevertheless, Hufanga is happy to be back after a long rehabilitation, which he experienced as positive on both a personal and professional level.

“For me, it was a chance to be with my family,” Hufanga said. “It was a chance to get into the script, into the movie theater. And so I never really looked at it as a bad process to go through. Everybody’s been through something, and I think this was just my story and my process. And so, when I looked at it, there were so many positives to the process versus the negatives, and I think a lot of people can get caught up in the negatives and that definitely affects your healing. … I’m just really happy to be back.”

Kittle, meanwhile, survived last week’s game against the Minnesota Vikings despite needing an IV at one point. If he can’t play against the Rams, the Niners would likely turn to veteran Eric Saubert to start in his place.

“I thought he did a great job,” Shanahan said. “He stepped in well. Kittle was cramping most of the game, so (Saubert) had to do a lot against Minnesota and he’s been very consistent since he’s been here. If he has to do everything, he’s up for the challenge.”

Jake Tonges is the only other tight end on the active roster, though Brayden Willis and Mason Pline provide options for the practice squad that could provide additional depth.

The Niners have rarely played without McCaffrey, Samuel and Kittle since McCaffrey arrived via trade in 2022. Quarterback Brock Purdy has started just 10 plays in 33 games without McCaffrey, Samuel and Kittle on the field. He is 3-of-7 for 49 yards with no touchdowns and an interception on those plays, though half of those came in mop-up duty against the Kansas City Chiefs in 2022 before Purdy was the starter.

On Thursday, Purdy was quick to point out that even if Kittle can’t play, the Niners still have plenty of options, including wide receivers Brandon Aiyuk and Jauan Jennings and running back Jordan Mason.

“It’s obviously a bummer when you don’t have your guys,” Purdy said. “It’s like, ‘OK, how do we get the ball to other guys?’ We have playmakers. I’ve said that before. We have a really good scheme, great playcallers and some great players that step up and do their jobs really well. I still have to do my job in terms of my reads and my progressions, more than I have to change how I think and make sure I get the ball to this guy or that guy because a couple guys are out. That’s not how it is.

“That’s the challenge for me, how can I get better with my progression and as a quarterback and approach situations, be as efficient as I can, no matter who’s in the game. That’s where my mindset is with this game. And obviously I’d love to have my guys back and play with them, but that’s just the way it is with this game sometimes.”