Villarreal will be without their two first-choice central defenders for the first leg of their Champions League semi-final against Arsenal on Wednesday.
Gonzalo Rodriguez and Juan Manuel Pena were injured during the 1-0 league defeat to Barcelona on Friday and have been ruled out of the Highbury encounter.
Pena is doubtful for the return leg in Spain next week after sustaining an injury to his left knee while Rodriguez, who tore a ligament in his left ankle, is out for the rest of the season.
This is a further blow to coach Manuel Pellegrini as he will also have to do without regular goalkeeper Sebastian Viera, who serves a one-match ban. He will be replaced by Mariano Barbosa.
Defensive midfielders Alessio Tacchinardi and Cesar Arzo could be handed the responsibility of marking Arsenal striker Thierry Henry, with both players set to be deployed in unfamiliar roles at the heart of Villarreal's defence.