La Roja have had to make do without Gerard Moreno for their opening two matches due to muscular discomfort, but the Villarreal man is thought to have a good chance of returning here and could be handed a start up top if Alvaro Morata is granted a rest.
Sporting Lisbon starlet Pedro Porro will hope to keep his place on the opposite flank, while Diego Llorente only lasted 45 minutes against Georgia and could be replaced by the returning captain Sergio Ramos.
Two more changes in the engine room could see Rodri and Koke provide fresh legs as Sergio Busquets and Fabian Ruiz drop out, but Pedri produced a stellar performance at the weekend and will not want to relinquish his spot in the team.
Dani Olmo's stunning winner at the weekend should be enough to see him return to the left-hand side over Bryan Gil, meaning that Mikel Oyarzabal will have to make do with another outing as a substitute in Seville.
Spain possible starting lineup:
Simon; Porro, Ramos, Martinez, Alba; Rodri; Torres, Koke, Pedri, Olmo; Moreno