Manchester United goalkeeper David de Gea replaces Iker Casillas - who played in La Roja's 2-1 win against Slovakia - in between the sticks for only his sixth cap for the incumbent European champions.
Macedonia, bottom of the group, also make widespread changes from their shock 1-0 defeat in Luxembourg as Vladica Brdarovski, Kirce Ristevski, Stefan Askovski, Ferhan Hasani and Marjan Radeski come into the side.
Macedonia: Pacovski, Brdarovski, Sikov, Ristevski, Zhuta, Gligorov, Petrovikj, Radeski, Hasani, Askovski, Ivanovski
Spain: De Gea, Carvajal, Ramos, Pique, Bernat, Busquets, Cazorla, Isco, Mata, Silva, Costa
Follow all the action from the game at the Nacionalna Arena Filip II Makedonski with Sports Mole's live text commentary.