The Portuguese midfielder took a kick just above his knee and boss Roberto Di Matteo has confirmed the player will have to sit out the trip to Villa Park.
There is better news though concerning Branislav Ivanovic, who has shaken off a groin strain and will be fit to play if selected.
"Ivanovic will be available for tomorrow, he has come through training fine," Di Matteo revealed in his pre-match press conference.
"The only doubt is Meireles who picked up a knock the other night, everybody else is okay. He's got a knock just above his knee so it shouldn't be too serious but he's not ready for tomorrow."
Di Matteo made six changes against Benfica on Tuesday night and he looks set to tinker again in an attempt to come up with a winning formula.
"I was trying to select a team that could play a good game against Benfica and the same will happen tomorrow, considering the strengths and weaknesses of Aston Villa," he added. "It's not a question of how may players we change, you look at how they are, their level of fitness, and select a team.
"It doesn't mean whoever misses one game will be in the next game. I am happy we have almost a full squad to select from which will be important for the run-in for us, but every individual game we have to look at which players will be best."