Pepe's knee injury will force changes in the Real Madrid defence for the visit of Real Zaragoza on Saturday, with Argentine Ezequiel Garay his most likely replacement.
Centre-back partner Raul Albiol bruised his shoulder during training on Thursday and is a doubt, but Christoph Metzelder has returned to work with the group after three weeks on the sidelines. Midfielder Xabi Alonso is suspended, while Kaka, Guti and Ruud van Nistelrooy are injured.
Stand-in Zaragoza coach Jose Aurelio Gay has a daunting task at the Bernabeu, where Real have a 100 percent record this season. His side have slipped into the relegation places, have the worst defensive record in the league and have yet to win away from home.
Striker Frederic Kanoute and defender Ivica Dragutinovic are back in contention after injuries when third-placed Sevilla host Getafe on Saturday.
Brazilians Adriano Correia and Luis Fabiano are still struggling with muscle and ankle injuries respectively.
Fourth-placed Valencia have doubts over midfielders Carlos Marchena and Pablo Hernandez, who both picked up knocks during their 2-1 Europa League win away to Genoa on Thursday.
Valencia visit sixth-placed Deportivo La Coruna on Sunday.
Atletico Madrid have doubts over their in-form duo of Jose Antonio Reyes and Sergio Aguero for their trip to face Tenerife on Sunday. Winger Reyes strained his neck last week while Argentine striker Aguero is recovering from a muscle injury.
Almeria coach Hugo Sanchez is under pressure to turn around his side's slump in form away to struggling Espanyol on Sunday, after the club president refused to give him his full backing last weekend. The sides are level on points in 16th and 17th.
Mauricio Pochettino's Espanyol have lost five on the trot without scoring a goal.
