France striker Benzema missed the visit of Borussia Dortmund in the Champions League on Tuesday with a thigh muscle problem and Argentina's Higuain was forced out at half-time in the same match with what looked like a hamstring injury.
"I don't think Benzema or Higuain will be available this weekend," Mourinho said after the 2-2 draw at the Bernabeu.
Levante, who lie sixth in the standings three points behind Real in third, upset the visitors 1-0 in September last year when Sami Khedira was sent off and Arouna Kone scored the game's only goal.
Two years ago, newly-promoted Levante held Real to a 0-0 draw there and also surprised Mourinho's men 2-0 in a King's Cup last-16 first leg, though they ended up losing 8-2 on aggregate.
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