Deebo Samuel got the ball on the 49ers' first offensive play, but appeared to come up lame at the end of the play.
The second-year wideout left the game flanked by trainers after the handoff from Nick Mullens, and the 49ers ruled Samuel out against the Washington Football Team early in the third quarter with a hamstring injury.
The 49ers initially announced Samuel was questionable to return, but didn't feel comfortable letting him return to the game.
Samuel has been plagued by injuries this season, and was making just his seventh appearance of the season for the 49ers.
Considering that the 49ers are 9-2 when Deebo catches four or more passes, coach Kyle Shanahan's offense very much would have liked to get the versatile playmaker back in the game, but that won't happen.
After each team's first drive ended in a punt, Samuel was seen on the Fox broadcast coming back from commercial in a 49ers hat and with his shoulder pads unhooked, an early indication that he wasn't going to return to the game.