Vicente del Bosque's men are the reigning World and European champions and currently sit atop the FIFA world rankings.
Equatorial Guinea, meanwhile, are 119th and without a victory in five matches. Their highest ranked opposition in that run was Tunisia, who sit 47th.
The outlook, then, is not good for the hosts, as they welcome a Spanish side who have lost just one of their last 32 fixtures - a 3-0 defeat to Brazil in the FIFA Confederations Cup.
The African nation finished bottom of their 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.
Spain are also set to face South Africa on Tuesday, and Real Madrid defender Sergio Ramos is hoping the fixtures can kick-start preparations for Brazil 2014.
"Our national team is feeling full of confidence, with a great deal of desire," Ramos is quoted as saying by Eurosport.
"We managed it before (winning the World Cup) and who's to say we cannot repeat that success.
"We cannot live on past achievements, there is no point dwelling on them, instead we want to repeat them."
