The junior forward was injured during practice Thursday.
"It's a severe knee injury," Arkansas coach Mike Anderson said on his pregame radio show. "We're going to have some further examination done to determine the extent.
"It's a tremendous loss for a guy who has worked extremely hard to get in the best shape of his career."
Powell has battled injuries throughout his career at Arkansas. He missed the entire 2010-11 preseason and three games last year with a broken foot, which he reinjured last spring.
The Virginia Beach, Va., native was averaging 19.5 points and 6 rebounds this season for the Razorbacks (2-0).