Samuel exited the game after the first offensive play of the game and was later ruled out with a hamstring injury.
"It happened the first play and you could -- just talking to him -- I know (he'll have an) MRI and we'll look at it tomorrow but it didn't look good," Shanahan said.
Samuel entered Week 14 having already missed six full games this season. He missed the first three while recovering from a Jones fracture suffered in June and then another three with a hamstring strain.
"We lost a pretty big element but it's not why we lost today," Shanahan added. "I mean, with the way our defense played. Obviously, Deebo is a huge part of us and would have helped a ton but that wasn't why we lost."
Shanahan also provided the following injury updates:
- Linebacker Fred Warner left the second half with a stinger and did not return.
- Running back Raheem Mostert was examined for head and ankle injuries but did return.
- Left tackle Trent Williams was examined for a knee injury but did return.