Head coach Kyle Shanahan addressed the injury during his postgame press conference but didn't express immediate confidence in the severity of the situation.
"We're not sure. Possible foot sprain," Shanahan said. "X-rays didn't for sure show anything, so we'll have to look into it more tomorrow."
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Despite the uncertainty, Guerendo sounded upbeat when speaking to reporters after the game.
"Yes, everything is fine," Guerendo said. "They're just being cautious. We have a quick turnaround this week, so we're just making sure that we're good to go."
The 49ers face a short week as they prepare to host the Los Angeles Rams at Levi's Stadium on Thursday night.
Guerendo left Sunday's game with just over six minutes remaining, heading to the medical tent before being escorted to the locker room. The running back finished the day with 78 yards and two touchdowns on 15 carries, along with two receptions for 50 yards.
The game marked Guerendo's first NFL start, stepping up in the absence of Christian McCaffrey and Jordan Mason, both of whom landed on injured reserve.
If Guerendo cannot suit up on Thursday, Patrick Taylor is expected to take the lead in the backfield.
"When we've given Patrick runs, going back to the preseason and in practice, he's a good runner," Shanahan noted. "He hits the right spots, he runs hard. So he's a guy who can definitely help us."
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