Tom Pelissero of NFL Network reported the news, noting that "further testing will tell the full story."
Guice took a hit to his left leg and needed attention from the team's medical personnel. He was initially listed as questionable before being downgraded to out.
Entering Sunday, Guice had rushed 37 times for 203 yards and two touchdowns in four games.
Knee injuries have curtailed the beginning of Guice's promising pro career, which began after the Skins drafted the LSU product 59th overall in 2018.
A torn ACL suffered in his first preseason game prematurely ended his rookie year. Guice emerged as the team's starting running back to begin 2019, but a meniscus injury suffered during Week 1 against the Philadelphia Eagles sidelined him for eight games.
This is also Guice's second knee injury of the season, having gone on injured reserve after knee surgery in September.
Without Guice, Washington will turn to Adrian Peterson, who the team acquired when the ex-Tiger suffered the torn ACL in 2018.
The 13-year veteran, who eclipsed 1,000 rushing yards for the eighth time last season, has amassed 4.4 yards per carry in 2019. The ex-Minnesota Viking and New Orleans Saints had also scored two touchdowns entering Sunday and added a third against the Packers on Sunday.
Chris Thompson should be the team's passing-down back. The 29-year-old has 28 receptions for 291 yards in addition to rushing for 3.6 yards per carry.