The Gunners now sit seven points behind fourth-placed Manchester City, with Arsenal having seven more games to try and uphold their impressive run of qualifying for the Champions League.
Shakespeare has injury problems to contend with, as Wes Morgan (hamstring) and Islam Slimani (groin) are still sidelined.
Boss Craig Shakespeare had hoped it was cramp but he will now be without the centre-back for Wednesday's clash at the Emirates Stadium.
When asked if it was his intention to make Vardy his main striker, Wenger said: "No, he was one of the strikers available".
"It's about rolling your sleeves up and making sure you turn those indifferent performances into good performances and you see the Jamie that we're seeing out here at the moment, playing full of confidence but a goal threat as well".
Mendy, a £13million signing from Nice last summer, has made just nine appearances this season after initially injuring his ankle in the 0-0 home draw with Arsenal in August. He had a floating bone in there that needed looking after.
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Leicester endured a horrid start to the season and parted company with manager Claudio Ranieri in February.
Leicester, now 15th in the league, have picked up five victories in their last seven league games to move six points clear of the relegation zone.
"I am reluctant to say he is back to his best, as I want more from him, but his goalscoring of late has been very good". I'm sure the owners and the board are aware of that'.
Leicester manager Craig Shakespeare believes Arsenal's FA Cup semifinal performance dispelled any notion of slumping.
He added: "Seeing the Arsenal match it didn't look like turmoil to me, there were players fighting and they thoroughly deserved the win in the end, even though it was a close game".
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