Wide receiver Deebo Samuel, who suffered a calf strain against the Minnesota Vikings, will also be unavailable for the matchup.
"Those are great players that are tremendous assets for them," Rams head coach Sean McVay said Wednesday per the team's official transcript. "[Head coach] Kyle [Shanahan] does a great job of being able to utilize the versatile skill sets that both of them have and the multitude of issues that they can present to put pressure on a defense. They have a lot of other guys that they do a great job doing that with as well."
Running back Jordan Mason has stepped in for McCaffrey, rushing for at least 100 yards in each of his two starts. Meanwhile, wide receivers Brandon Aiyuk and Jauan Jennings will be counted on to fill the void left by Samuel's absence.
"You still have a movable piece in [FB Kyle] Juszczyk," McVay continued. "[TE George] Kittle and Aiyuk are nightmares, and I think Jauan Jennings is a very underrated player. You've seen [TE Eric] Saubert makes some plays and then obviously their offensive line. [Offensive line coach/run game coordinator] Chris Foerster does as good a job as anybody of getting those guys ready to roll."
The Rams have lost their last six home games against the 49ers and are eager to end that streak on Sunday. Despite missing key players, the 49ers are favored by seven points in the matchup.
"It's a challenge," McVay said. "It's really a challenge with those two guys out. Hopefully, they'll be okay, but I'm not sad that they're not playing against us. They are still as good as it gets offensively in this league."
The Rams will also be without several star players. Wide receiver Puka Nacua is on injured reserve due to a PCL sprain, while Cooper Kupp is expected to miss extended time with an ankle injury. Their offensive line is also dealing with injuries.
One player the 49ers are relieved they don't have to face anymore is recently retired defensive tackle Aaron Donald. When asked about playing the Rams without Donald, wide receiver Brandon Aiyuk said, "It's great. It's great."
Defensive lineman Nick Bosa acknowledged Donald's remarkable career, calling him a "dominant" force.
"He was the best in the game for 10 years, and then called it, got out healthy," Bosa added. "That's what everybody's dream is. It's been fun to watch him, and we're glad we don't have to play him anymore."
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