Johan Djourou joined an injury list that includes Bacary Sagna (ankle), Kieran Gibbs (hernia), Andre Santos (ankle) and Carl Jenkinson (back) when he suffered a groin strain during Sunday's 1-0 loss to leaders Manchester City.
Djourou is now set to be out for three weeks and either Sebastien Squillaci or Ignasi Miquel could start at Villa Park.
Arsenal are also already without players in other areas such as Jack Wilshere (ankle), Lukasz Fabianski (knee), Vito Mannone (shoulder) and Abou Diaby (hamstring), while Alex Song is suspended.
Gibbs, 22, has recently suffered a fresh setback after being sidelined for the past two months following his hernia operation.
"Kieran Gibbs has unfortunately had a setback and he is not back yet," Arsenal manager Arsene Wenger told Arsenal.com.
"It's very disappointing because we had good hope that he would be back for tomorrow's (Wednesday's) game, but he is not available."
But Wenger had more encouraging news regarding the fitness of teenage Japanese forward Ryo Miyaichi who has been sidelined with an ankle injury.
"Ryo is joining in normal training on Friday, so he is completely back from injury," Wenger said.
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