Maniscalco has been dealing with a re-occurring left ankle injury for much of the season, which kept him out of Wednesday's game with Northwestern. He's had two surgeries on the ankle in the past two years.
Maniscalco has played in 15 games, starting 13, and has averaged 9.9 points, 2.4 rebounds and 2.9 assists.
"We got him in the boot right now, and we're trying to rest him," Illinois coach Bruce Weber said. "If he comes to me tomorrow morning, 'Coach, I want to give it a go,' we could consider it. But I would say he's probably doubtful.
"I just feel bad for Sam. We knew he had had surgeries, and he had bone spurs. I think when it comes down, he's just a kid who goes so hard, and he's gone hard his whole life. Your body can only take so much."
Richardson injured his right wrist during the second half of Wednesday's win over Northwestern. He had an X-ray taken, and there was no fracture.
Richardson has started all 16 games this season and leads in scoring at 13.9 points per game and with 41 3-pointers.
"He had landed on his wrist, and he had already hurt it in practice," Weber said. "It's very sore and stiff. [Director of sports medicine Al Martindale] is working hard. He got in a little bit of practice today.
"We'll see how tough he is. The one thing I told him is maybe he can't score a point with that wrist, but he can guard and help us. Even if we win 30-29, I know we'll make national headlines, but who cares?"
Scott Powers covers high school and college sports for ESPNChicago.com and can be reached at firstname.lastname@example.org.