Varane, 20, has been unable to train for two days with Didier Deschamps' squad, as they prepare for Friday's first leg in Kiev.
The central defender has played just six matches for Real Madrid this season, after his breakthrough 2012-13 campaign, and Deschamps has conceded it is unlikely Varane will take the field.
Deschamps could not resist a dig at Madrid either, blaming them for Varane's injury after he was picked to play 90 minutes against Juventus last week and then versus Real Sociedad on Saturday.
"His knee is inflamed and so he's been taking it easy, we are closely monitoring his situation," he said.
"I think it's a direct result of playing two games in three days with Real Madrid."
Deschamps had hoped to pick Varane alongside Monaco's Eric Abidal in the centre of defence, but is now expected to deploy Laurent Koscielny instead.
The second leg of the World Cup play-off for a spot at Brazil 2014 will be held in Paris on Tuesday.
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