Iker Casillas, David Silva and Fernando Torres came into the Spain line-up for Thursday's Confederations Cup semi-final in Fortaleza against Italy, who recalled the fit-again Andrea Pirlo.
Spain used three different goalkeepers in their group-phase matches, but coach Vicente del Bosque placed his faith in captain Casillas for the game at Estadio Castelao.
Silva and Torres, the tournament's top scorer with five goals, came in for Cesc Fabregas and Roberto Soldado, both of whom sustained muscular injuries in Sunday's 3-0 win over Nigeria.
Italy have been beset by injuries and coach Cesare Prandelli made six changes to the team beaten 4-2 by Brazil in their final Group A game, notably flooding his line-up with midfielders.
Pirlo, who missed the Brazil game with a calf injury, was named in central midfield alongside Daniele De Rossi, who returned from suspension.
Christian Maggio took over as right wing-back from Ignazio Abate, whose tournament was ended by a dislocated shoulder, while Bologna striker Alberto Gilardino led the line in place of the injured Mario Balotelli.
World champions Spain won 4-0 the last time the two sides met, in the final of Euro 2012 last year.
The winners of Thursday's match will face hosts Brazil in the final at Rio de Janeiro's Maracana on Sunday.
Starting line-ups in the Confederations Cup semi-final between Spain and Italy at Estadio Castelao in Fortaleza on Thursday (1900GMT kick-off):
Iker Casillas (capt); Alvaro Arbeloa, Gerard Pique, Sergio Ramos, Jordi Alba; Sergio Busquets, Xavi, Andres Iniesta; Pedro Rodriguez, David Silva, Fernando Torres
Coach: Vicente del Bosque
Gianluigi Buffon (capt); Leonardo Bonucci, Andrea Barzagli, Giorgio Chiellini; Christian Maggio, Daniele De Rossi, Andrea Pirlo, Emanuele Giaccherini; Claudio Marchisio, Antonio Candreva; Alberto Gilardino
Coach: Cesare Prandelli
Referee: Howard Webb (ENG)