Wilfred Bouma is set to undergo further ankle surgery which will rule him out for the remainder of the season.
Villa boss Martin O'Neill is already resigned to losing captain Martin Laursen for the rest of the campaign with the knee problem which has sidelined him since early January.
Now Bouma looks set to follow suit after battling in vain to return from the dislocated ankle suffered during the Intertoto Cup clash with Odense BK at Villa Park in late July.
The Dutch international had looked on course to play some part in the run-in after completing three games for the reserves.
O'Neill said: "Freddie has had a bit of a setback. There have been some floating particles in the ankle that might have been there for some time or might have broken off in his rehab.
"I think he needs a bit of keyhole surgery. If he does, I think that might prevent him from making the comeback between now and the end of the season.
"We will know better about that by the middle of next week but I think the idea is that it is best to get it (the surgery) done now."
Villa have particularly missed Laursen and conceded 24 goals in their last 10 games as their Champions League hopes have nose-dived.
But Bouma has also been a massive loss and his replacement, Nicky Shorey, has found himself out of the side for most of the second half of the campaign before earning a recall for the last two matches with Manchester United and Everton.
O'Neill has preferred to play right-back Luke Young on the opposite flank rather than former Reading player Shorey, who made the £5million switch to Villa Park in August.