Vicente del Bosque's men are the reigning World and European champions and currently sit atop the FIFA Ranking.
Equatorial Guinea, meanwhile, is 119th and without a victory in five matches. The team's highest ranked opposition in that run was Tunisia, which sits 47th.
The outlook is not good for the home side as it welcome a Spanish team that has lost just one of its last 32 fixtures - a 3-0 defeat to Brazil in the Confederations Cup.
The African nation finished bottom of its World Cup qualifying group without recording a single victory, while Spain edged out France to progress automatically from the European campaign.
Diego Costa - Atletico Madrid's Brazil-born forward who was tipped to make his debut for Spain - has been forced to withdraw from the squad with a torn muscle in his right leg, and he joins Cesc Fabregas (knee) on the sidelines.
Fernando Llorente and Marc Bartra have been called up as replacements, with the latter hopeful of making his senior debut on Friday.
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