It was reported early Friday that the initial diagnosis was a sprained MCL, but a subsequent MRI revealed the full extent of the injury.
Selected in the second round of this year's draft, former LSU standout Guice went down awkwardly as he was tackled from behind on an impressive 34-yard scamper negated by a holding penalty.
The injury is devastating news to the Redskins, who drafted Guice to fix their 28th-ranked run offense from 2017.
Guice hyperextended his left knee at LSU last season but was held out of only one game. Washington will now rely on Rob Kelley and Samaje Perine to be their primary backs, while Chris Thompson will continue his role as a third-down specialist.
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It's a major blow for the Redskins going into a critical season for Jay Gruden's offense directed by new quarterback Alex Smith.
But now, Guice will spend the 2018 season rehabbing. But there are other running backs, such as Ronnie Brown and Edgerrin James, who were never the same after the injury.
"Playing late into the season the year before is definitely what we want to do, so we're not complaining about that, but it does affect the following season, there's no question about that", he said.
A star rookie running back reportedly suffered a knee injury during the first half of a preseason game on Thursday night.