Leaders Barcelona will be without injured defensive trio Carles Puyol, Gerard Pique and Dani Alves who were all left out of the squad to visit promoted Deportivo La Coruna on Saturday.
Midfielders Alex Song and Javier Mascherano could reprise their central defensive partnership, though full-back Adriano Correia was a surprise choice at centre-back for the 'Clasico' two weeks ago.
"We thought Pique would be ready for the Depor game but he isn't 100 percent," Barca coach Tito Vilanova told a news conference on Friday. "We didn't risk him against Real and we won't tomorrow either."
Barca hold an eight-point lead over fifth-placed champions Real, who host promoted Celta Vigo on Saturday.
Jose Mourinho's side lost full-backs Marcelo, Alvaro Arbeloa and Fabio Coentrao to injury during the break for internationals and, like Barca, will need to shuffle their defence to cover at left-back.
Unbeaten Atletico Madrid may have the chance to go top when they visit Real Sociedad on Sunday, if leaders Barca slip up in La Coruna. They are level on 19 points but second on goal difference.
Coach Diego Simeone is likely to be without Turkey playmaker Arda Turan who returned from international duty with an ankle injury.
Third-placed Malaga host promoted Valladolid on Saturday with a doubt over Spain full-back Nacho Monreal who has a back complaint and Argentine striker Diego Buonanotte, who has a knee ligament problem.
Long-term injury victim Julio Baptista, who is recovering from Achilles surgery, started doing ball exercises on Thursday for the first time since his operation.
Misfiring Valencia have midfielders David Albelda, Ever Banega and defender Ricardo Costa back in the squad after injury as they prepare to host another struggling side, Athletic Bilbao, on Saturday.
"Bilbao are in a similar situation to us, looking for some consistency and a run of wins to get back up the table," Brazil forward Jonas told a news conference.
Bottom club Espanyol have taken two points from a possible 21 so far and, after fan protests against the team and the board at their last home game, coach Mauricio Pochettino is under pressure for the visit of Rayo Vallecano.
"If we don't win on Sunday it will be me that has problems," Argentine boss Pochettino told Radio Marca.
Real Zaragoza visit Granada on Sunday without Serbian defender Ivan Obradovic who requires surgery on a knee ligament injury. He is expected to be out for around six months.
