Guice injured his left knee at the end of a first-quarter run during Thursday's preseason opener against the New England Patriots.
A second-round draft choice out of LSU, Guice had 19 yards on six carries before leaving the game. He hung around the locker room with teammates after the Redskins' 26-17 loss, sucking on a lollipop at his locker as he scrolled through his phone.
He later walked from the locker room to the team buses, and there was a noticeable stiffness in his stride.
On Saturday, Redskins coach Jay Gruden said the team is confident in the remaining running backs on the roster -- Rob Kelley, Samaje Perine, Chris Thompson, Kapri Bibbs and Byron Marshall -- and that Washington doesn't plan to sign a veteran at this time.
Gruden said the Redskins might end up with a running back-by-committee approach.
"We have guys in here," Gruden said. "We drafted Derrius because he was the best player, not because we weren't satisfied with the backs we have. We're pretty good at the running back spot.
"We'll have it covered, no problem, but we are disappointed."
Thompson, who suffered a season-ending leg injury in 2017, tweeted Friday that the news Guice was out for the season hit him hard.
Had a tough time tryna hold back the tears this morning when I got the news. We had something great going in our room but you know the squad got you every step of the way bro. Heal up and get ready to take over the league next year. @DhaSickest pic.twitter.com/3bHv3Oh8Ql— Chris Thompson (@ChrisThompson_4) August 10, 2018
He choked up while talking about Guice on Saturday, saying, "It was just a tough situation, man. He came into the facility with his brother [Friday] and his brother was crying.
"[Guice] has been through a lot, to just see him go down before the season even got started, before he can even get a taste he's already down. It's just tough. ... This is my first time ever shedding tears for a player. Our group has become so close to each other in a short period of time, just to see one of the guys going down. I feel like that's my little brother; that's my dude. To see him go down was a terrible feeling."
Guice sprained his left knee at LSU last season but missed only one game. He has made a quick first impression on his Redskins teammates, including backup quarterback Colt McCoy, who said Guice has been "fun to watch" and is a "great player."
Guice's character was knocked before and during the draft process, but the Redskins had been pleased with his conduct. They said he was attentive in meetings and asked good questions.
On the field, teammates raved about what he might do, with Thompson saying he wanted Guice to rush for 1,200 yards. His engaging personality won over fans as he stayed late after most practices to sign autographs. Guice had been one of the Redskins' most anticipated rookies among the fan base, certainly since Robert Griffin III in 2012.
"It's heartbreaking," Redskins tackle Trent Williams said Saturday. "Not only for the team because that was a major asset that we had planned on contributing to winning games, but to the person. He just accomplished his lifelong dream to be in the NFL and to suffer a setback in his first game ... I hate that it happened to him."
"You miss a guy like that," Williams continued. "On days like this where it's hot, it's muggy, attitudes are everywhere and guys have been in Richmond [Virginia, site of training camp] too long and practice gets stale, you got a guy like Derrius who is always in a good mood. You can always look to him to pick you up; you know you'll get a laugh out of him. He lightens up the situation. Not having a guy like that around the team, we'll definitely miss him."
Gruden said the Redskins will miss what Guice offered.
"He's an explosive player," Gruden said. "What we didn't know about him is what he didn't do at LSU were his hands, catching the ball. His pass-blocking skills were pretty darn good. He picked up a safety blitz the other night. We were very impressed with his total package, not just his running skills. We will continue to be impressed, and he'll be stronger when he comes back than he is now."
Information from ESPN's Mike Reiss and John Keim contributed to this report.