Jack Ross admits it would be a major blow to lose Charlie Wyke for any period of time after he was stretchered off in the 2-1 defeat to Burton Albion.
The striker has injured the same knee that kept him out at the start of the season, with the former Bradford City striker only just back from that injury.
He injured his right knee after a collision with Burton keeper Dimitar Evtimov in the first half and had to be stretchered from the field, Wyke visibly upset.
Ross says the striker will be assessed over the next 24-48 hours and is praying for the best, though he admits any lengthy spell out would be a major blow.
The Sunderland boss said: "There was a significant impact when he challenged with their goalkeeper.
"It is the same knee that he came to the club with, he is in a bit of pain right now.
"Sometimes these things can settle quite quickly and they are not as bad as you believe but it can go the other way.
"We'll be assessing it over the next 24-48 hours.
"For him, it is a blow because he is just working his way back to full match sharpness. We felt we needed to start him in games as well, to pick up an injury so early is frustrating for him."
Wyke missed the start of the season with knee ligament damage.
Ross added: "We don't know what the injury is yet, it is the same knee, I don't know whether it is just impact or whether there has been a twist.
"It had settled down a bit at half-time but he was still sore."
The Sunderland bench appeared unhappy with referee Dean Whitestone during the game for not sanctioning the Burton keeper.
But Ross admits on reflection he didn't think it was anything more than an unfortunate collision.
Ross said: "At the time I thought it was perhaps reckless but I have watched it again and I think it is just a collision.
"I can't have too many complaints about it. I think the one on Lynden [Gooch] in the second half was worse.
"In fact it was worse. The one in the first half, it was probably just a collision.
"He is in a bit of pain, Charlie, we have to let it settle and assess where he is. It would certainly be a blow for us and the squad.
"He has worked hard to come back, he has been playing catch-up. It would be even more frustrating if he had to start again in that sense."