The 29-year-old felt discomfort in his right ankle and travelled to Porto for a consultation on Wednesday morning which ended in doctors deciding on medical intervention.
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|4/1||Real Madrid are 4/1 to win the Champions League with William Hill|
The first leg of Real's last-16 tie will take place at the Santiago Bernabeu, with the return leg scheduled for March 5 at Old Trafford.
Pepe has played a crucial role for Los Blancos so far this term, making 16 league appearances for Jose Mourinho's side.