The 31-year-old has been in excellent form for the Yellow Submarine this season, scoring six goals in his opening seven La Liga matches, but he was absent last time out through injury.
Perez was not able to train on Thursday, meaning that he is a major doubt for the trip to Real Madrid, while Denis Suarez could also miss out with the issue that forced him off against Las Palmas.
Willy Kambwala, Gerard Moreno, Juan Foyth and Alfonso Pedraza are also definitely absent through injury, so head coach Marcelino will have a number of injury issues for this clash.
Alex Baena is expected to replace Suarez in the XI following the clash with Las Palmas, but it might otherwise be the same side that took to the field for the first whistle.
Nicolas Pepe scored his first goal for the club while operating through the middle against Las Palmas, and that could again be the case this weekend, with Ilias Akhomach operating in a wide area.
Thierno Barry has scored twice in seven La Liga appearances for Villarreal this season, and he should again feature through the middle at Bernabeu, while there is again expected to be a position in the middle of the park for experienced midfielder Dani Parejo.
Villarreal possible starting lineup: Conde; Femenia, Bailly, Costa, S Cardona; Akhomach, Parejo, Gueye, Baena; Barry, Pepe
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