Asenjo injured his knee when he landed awkwardly after jumping for a ball in Wednesday’s 1-0 home defeat by Atletico Madrid.
“Asenjo has ruptured the anterior cruciate ligament of the right knee, along with less serious injuries and they will require surgery,” the club said in a statement on their website.
It is the latest injury setback for Villarreal whose results have suffered with the team falling well away from Champions League contention and they now lie sixth in La Liga on 53 points from 34 games.
Key players Bruno Soriano and Mateo Musacchio have both had serious problems while Denis Cheryshev and Luciano Vietto, who spearheaded their strong early season form, have suffered minor injuries.
(Reporting by Tim Hanlon, editing by Pritha Sarkar)
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