An ongoing Achilles tendon problem caused the captain to fail a Thursday morning fitness test and he will now sit out Friday night's game at the Aviva Stadium.
The LA Galaxy striker sat out training on Wednesday, but he had been hopeful of making the game.
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"I've had a problem with my Achilles for a while," the striker told the Irish Times.
"I got a kick on it yesterday [Tuesday] in training and it has swollen up. I've had a scan on it and I'll see how it goes tomorrow at training. It's a bit sore but I hope to play."
Stoke striker Jon Walters appears the favourite to lead the line in Keane's place, in what would be his 11th international appearance.