Ivan Rakitic will replace the suspended Sergio Busquets in the defensive midfield role for Barcelona at Celta Vigo on Saturday, while Arthur could also start despite his imminent transfer to Juventus.
Busquets picked up a yellow card in the 1-0 win at home to Athletic Club on Tuesday and misses the trip to Balaidos with a ban.
Rakitic replaced the Spanish international against Athletic in the second half and scored the only goal of the game at Camp Nou.
With Frenkie de Jong out because of a calf problem, the Croatian will feature as the deepest midfielder on Saturday.
Arthur, who has agreed to join Juventus in a deal which will see Miralem Pjanic move the other way, could also start in Galicia.
Riqui Puig is another alternative for Setien after the youngster came off the bench and changed the game on Tuesday.
Sergi Roberto is still out with a fractured rib, so Nelson Semedo will continue at right-back.
Antoine Griezmann is expected to keep his place alongside Lionel Messi and Luis Suarez, with Ansu Fati on the bench after his impressive cameo against Athletic.
Barcelona are level on points with Real Madrid with seven rounds remaining in LaLiga, but behind Los Blancos - away to Espanyol on Sunday - in the head-to-head record in the two Clasico clashes this term.
Celta Vigo predicted XI: Blanco; Murillo, Araujo, Aidoo; Vazquez, Yokuslu, Bradaric, Olaza; Rafinha, Suarez; Aspas
Barcelona predicted XI: Ter Stegen; Semedo, Pique, Lenglet, Alba; Arthur, Rakitic, Vidal; Messi, Suarez, Griezmann
