Gabby Agbonlahor, Antonio Luna and Joe Bennett are all set to miss Saturday's Barclays Premier League clash against West Ham.
Agbonlahor is struggling with an ankle injury and the Hammers encounter is set to come too soon for the 27-year-old striker.
Luna could be out of action for a couple of weeks with a hamstring problem he sustained in last weekend's defeat to Everton.
And fellow left-back Bennett has also been ruled out with a back injury.
"Gabby is a doubt," said manager Paul Lambert.
"His ankle has not really recovered from when he first got it injured.
"Antonio is struggling with his hamstring at the minute. He'll be a few weeks out.
"Joe Bennett has a sore back at the minute so we'll see how he is."
Lambert has challenged his fringe players to seize their opportunity with places up for grabs in the starting XI.
"It is a chance for everybody," the Villa boss added.
"You get an injury and someone else comes in. It is up to them to step up.
"That's football all the time. Someone else's miss fortune is somebody else's gain.
"You have to take the chance and whoever comes in, I'm pretty sure they won't let anybody down."
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