Sergio Busquets has been left out of Barcelona's squad for Saturday's match at Rayo Vallecano, the club said on Friday, opening the door for Alex Song or Sergio Roberto to start in midfield.
Coach Gerardo Martino, who replaced Tito Vilanova in the close-season, has sought to keep his squad fresh by resting and rotating players who have also had international commitments.
Busquets was left off the squad list released by Barca, who are seeking a fifth straight league win against a Rayo side who are looking to end a three-game losing streak following their opening 3-0 victory against Elche.
Barca's assistant coach Jorge Pautasso was standing in at the pre-game news conference for Martino, who has travelled to Argentina to attend his father's funeral.
Pautasso defended Martino's attempts to alter the team's tactics and to reintroduce elements from former coach Pep Guardiola's successful side.
"We're not bringing any revolution, not even major changes," he told reporters.
"We would never betray the Barcelona style, since we want to add to, not take away from, the good that was achieved."
Rayo's main focus will be on tightening up at the back, having conceded 12 goals already this season, more than any other side in La Liga.
Barcelona are tied with Atletico Madrid as the league's most prolific scorers with 14.
Martino will return from Argentina on Saturday morning in order to be in the dugout in Madrid.
Lionel Messi is set to play his 250th La Liga game, nine years after making his debut against Espanyol.