Guice flashed the skills that prompted the Redskins to take him in the second round of the 2018 NFL Draft, but he limped off the field with a knee injury during the preseason opener against the New England Patriots.
Washington coach Jay Gruden said after Thursday's game that Guice will undergo an MRI exam on Friday, although the former LSU standout downplayed the injury.
"I'm good," Guice said after the game. "All is well."
The NFL Network, citing a source, reported that Guice was initially diagnosed with a sprained medial collateral ligament.
Guice finished with only 19 yards on six rushing attempts in the Redskins' 26-17 loss, but it was a play that didn't count that drew the most oohs and aahs -- and resulted in the injury.
The 5-foot-11, 225-pound Guice broke off a highlight-reel 34-yard run that was negated by a penalty.
Guice made a quick cutback to break into the open, spun away from one defender and then stiff-armed another would-be tackler, but he was slow to get up and hobbled to the sideline.
"I can walk fine," Guice told the Washington Post. "I guess, at the back end of the play when I was still (fighting), my feet just kind of planted weirdly on the turf and my knee just hyperextended a little bit. It's fine."
Washington is expecting big things from Guice, who rushed for 1,251 yards and 11 touchdowns last season at LSU. He was even better as a sophomore, piling up 1,387 rushing yards and 15 touchdowns.
"Hopefully, it's nothing. But if it is, I'm sure Derrius will rehab it and get himself back," said Gruden, who revealed that Guice lobbied for a heavy workload entering his NFL debut.
"He's a guy that doesn't like to carry the ball three times. He needs to carry the ball 15 times," Gruden told the Post. "He actually told me before the game, 'If you're going to give to me three times, don't even put me in.'"