Madrid secured a 1-1 draw at the Stade Gerland and, having exited to Lyon at this stage last year, will have concerns about whether they can avoid an seventh successive second-round exit.
Having seen Ronaldo sustain a muscular injury during the 7-0 victory over Malaga, there were suggestions they could also be without their leading scorer.
Ronaldo did not train with his team-mates on Friday and, although he is apparently not experiencing pain, the club's medical staff have recommended that he be given extra time to make a full recovery.
He has therefore been left out of the squad for this weekend's game against Hercules, but Mourinho has indicated that the forward will be available for the crunch European tie.
"The match against Hercules is not the right time for him to return to match action, but I think that he'll be able to start against Olympique Lyonnais on Wednesday," he said.
"If he is able to train on Sunday, Monday and Tuesday then I believe he will play."
Writing on Twitter, Ronaldo had said on Thursday: "I am resting, and hope to be back soon."