The Brazilian-born frontman returns to the starting XI having been rested for Wednesday's friendly with Colombia, taking the place of Alvaro Morata despite the Real Madrid man having scored a late equaliser in Murcia.
Macedonia, meanwhile, have all-time leading goalscorer and captain Goran Pandev leading the line as he wins his 87th cap for his country.
Macedonia: Dimitrievski; Toshevski, Shikov, Mojsov, Ristevski; Ristovski, Stjepanovic, Spirovski, Alioski; Nestorovski, Pandev
Subs: Trajchevski, Gachevski, Mitov-Nilsson, Churlinov, Ibraimi, Trichkovski, Trajkovski, Atanasov, Elmas
Spain: De Gea; Carvajal, Pique, Ramos, Alba; Busquets, Thiago, Iniesta; Isco, Costa, Silva
Subs: Vitolo, Koke, Nacho, Deulofeu, Morata, Asensio, Aspas, Reina, Monreal, Pedro, Kepa, Saul