Hamstrung Given ruled out for a month
Given was substituted in the first half of Villa's 1-0 defeat by Manchester United on Saturday.
"It is disappointing to lose Shay in such circumstances but, unfortunately, these things happen in football," Villa manager Alex Mcleish said.
Given will be replaced by American Brad Guzan.
"We have to meet these challenges and we will," Mcleish added. "We have total faith in Brad."
The 35-year-old Given, Ireland's most capped player, helped his national team to qualify for next year's European Championships with victory over Estonia in last month's play-offs.