Yacouba Sylla and Chris Herd look set to miss Villa's Barclays Premier League opener at Arsenal.
Midfielder Sylla twisted his ankle in Monday's U21 game against West Ham and is a serious doubt for the trip to the Emirates.
It is hoped the Mali international will resume training next week.
Utility man Herd is still struggling with the calf problem he picked up during the pre-season friendly clash at Walsall on July 31.
"Yacouba has twisted his ankle so he'll be a doubt, which is a bit of a blow because he was a big player for us last year," said boss Paul Lambert.
"It is not too bad but he will probably miss this one. He might train later in the week but we will see how he is.
"Chris is the other one, then that is it. Everybody else is fit."
Lambert is yet to decide whether to hand new signing Jores Okore his competitive debut this weekend.
The Danish central defender is short of match practice after missing a large part of Villa's pre-season programme with a hamstring injury.
"Jores hasn't played a lot of games because of his injury in Germany," added the Villa boss.
"But we've still got another 24 hours to decide what to do.
"He's been excellent in the time he has been here but he is short of match practice at the minute."
Snap up your Sylla No.18 shirt now.