SANTA CLARA, Calif. — The San Francisco 49ers will likely be without three of their best offensive players and two of their best defensive players could be missing when they face the Los Angeles Rams on Sunday.

After tight end George Kittle (hamstring) missed practice on Thursday and Friday, his participation on Sunday was listed as questionable. If Kittle does not play against the Rams, he would be excluded as important offensive options alongside running back Christian McCaffrey (calf/Achilles tendinitis) and wide receiver Deebo Samuel (calf).

On the other side of the ball, defensive end Nick Bosa and cornerback Charvarius Ward, two of the Niners’ best defenders, are listed as questionable. Coach Kyle Shanahan said Bosa suffered a rib injury during a one-on-one matchup on Thursday and was limited in that practice and again on Friday. Ward also missed Thursday’s practice because of hamstring and knee soreness, but was a limited participant in Friday’s practice.

Kittle and Ward were surprisingly added to the injured list on Thursday after completing the entire practice on Wednesday.

“(Kittle) and Charvarius were sore after practice (on Wednesday), like a lot of others,” Shanahan said. “They came in Thursday morning and they were still sore. And Kittle is still sore today. That’s how bad it is.”

Better injury news for the Niners: Safety Talanoa Hufanga is cleared to play after tearing a cruciate ligament in his right knee. Hufanga was questionable for the first two weeks as he worked his way back into the team, but he hasn’t played against the Rams and is ready to start.

Shanahan said Hufanga is prepared for the game and how much he plays will depend on how things go from series to series. That means George Odum and Malik Mustapha could play as safety alongside Ji’Ayir Brown.

Nevertheless, Hufanga is excited to be back after a long rehabilitation that he has tried to view as positive both personally and professionally.

“For me, it was an opportunity to be with my family,” Hufanga said. “It was an opportunity to immerse myself in the script, immerse myself in the filming room. And so I never really looked at it as a bad process. Everyone’s been through something, and I think that was just my story and my process. And when I look at it, there are so many positives and negatives, and I think a lot of people can get caught up in the negatives, and that will impact their healing for sure. … I’m just really happy to be back.”

Kittle, on the other hand, played through last week’s game against the Minnesota Vikings despite needing an IV during the game. If he can’t play against the Rams, the Niners will likely replace him with the experienced Eric Saubert.

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

Jake Tonges is the only other tight end on the active roster, but Brayden Willis and Mason Pline offer practice squad options that could be added for more depth.

The Niners have barely played without McCaffrey, Samuel and Kittle since McCaffrey arrived via transfer in 2022. Quarterback Brock Purdy has had just 10 plays in 33 games without McCaffrey, Samuel and Kittle on the field. He has completed 3 of 7 passes for 49 yards with no touchdowns and one interception on those plays, although half of those came as cleanup work against the Kansas City Chiefs in 2022 before Purdy became the starter.

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

“Obviously it sucks when you don’t have your guys,” Purdy said. “It’s like, ‘All right, how do we figure out how to get the ball to the other guys?’ We have playmakers. I’ve said that before. We have a really good scheme, great playmakers and some great players that step into their roles and do their jobs really well. I still have to do my job as far as my reads and my progressions, more so than I have to change my mindset now and make sure I get the ball to this guy or that guy because a couple guys are out. It’s not like that.

“That’s the challenge for me: How can I continue to improve in terms of my progressions and my role as quarterback, and how can I handle situations, be as efficient as possible, no matter who’s there. That’s my attitude towards this game. And of course I’d like to have my guys back and play with them, but that’s just how it is sometimes in this game.”