The Portugal international has not featured for Carlo Ancelotti's side since their 2-2 draw with Atletico Madrid in the Copa del Rey on January 15, but he is back in contention for this weekend.
Real host Deportivo La Coruna at Santiago Bernabeu on Saturday, looking to recover from their 4-0 drubbing at the hands of Atletico in the league.
Pepe's return could add a stronger option at the back after Raphael Varane and Nacho struggled in the derby, however they will be without Fabio Coentrao.
The full-back played the full 90 minutes at Vicente Calderon, but now looks set for a period on the sidelines having suffered a calf injury during training.
Coentrao will undergo further tests on the extent of his injury before a decision will be made on when he is ready to return to first-team action.
