Chelsea trio Marcos Alonso, Cesc Fabregas and Alvaro Morata have all missed out on inclusion in Spain's squad for the World Cup.
Each player has endured an inconsistent domestic campaign with Chelsea missing out on the Champions League, and it has resulted in their omission from Julen Lopetegui's plans for the tournament in Russia.
Arsenal right-back Hector Bellerin is another high-profile absentee, but Gunners teammate Nacho Monreal has been selected in the 23-man squad.
Manchester United goalkeeper David de Gea, Chelsea defender Cesar Azpilicueta and Manchester City playmaker David Silva are all involved, as is departing Barcelona playmaker Andres Iniesta.
Spain face games against Portugal, Iran and Morocco in the group stages.
Full squad
Goalkeepers: David de Gea, Pepe Reina, Kepa Arrizabalaga
Defenders: Jordi Alba, Cesar Azpilicueta, Dani Carvajal, Nacho, Nacho Monreal, Alvaro Odriozola, Gerard Pique, Sergio Ramos
Midfielders: Isco, Thiago Alcantara, Sergio Busquets, David Silva, Andres Iniesta, Saul Niguez, Koke, Marco Asensio
Forwards: Iago Aspas, Diego Costa, Rodrigo, Lucas Vazquez
