Boss Unai Emery says Youri Tielemans' injury is "better than we expected", but the Belgian midfielder has been ruled out of the game at the Stadium of Light.
And Villa also face an anxious wait to see whether Victor Lindelof will be available.
The former Manchester United defender missed Tuesday night's Carabao Cup penalty shoot-out defeat at Brentford with a "small injury", and it's not clear at this stage when he'll be in contention to return.
There was better news on the injury front at Brentford, with Boubacar Kamara returning to the squad, and the 25-year-old is expected to be in contention to start on Wearside.
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But Villa will still be without the injured Amadou Onana and Ross Barkley, who is dealing with a personal issue.
Tielemans' continued absence - "maybe in one or two weeks he will be available", said Emery - is a major blow for Villa, who are short of midfield options. Evann Guessand and John McGinn have been playing as the two holding midfielders for Villa, who have become only the fifth side in Premier League history to not score a goal in their first four games of the season.
They did manage to hit the net at Brentford on Tuesday night, with Liverpool loanee Harvey Elliott putting them ahead in the first half. But the Bees hit back through Aaron Hickey just before the hour mark and Keith Andrews' side won 4-2 on penalties.
Emery said: "Of course, we need to improve, and we need to compete, and we need to get a result. But after Saturday in Everton and drawing today, scoring goals, I think we are watching some improvements.
"Not enough, the improvement we did today, but a lot of things, I think, will be positive for the next weeks, and, of course, for the next competition, Sunderland and Europa League."