Alvaro Morata has missed out on a place in Spain's squad for the World Cup in Russia, with Cesc Fabregas, Marcos Alonso, Ander Herrera and Hector Bellerin also omitted by Julen Lopetegui.
Lopetegui named his 23-man squad for the tournament on Monday, with four Premier League players included - David de Gea, Cesar Azpilicueta, Nacho Monreal and David Silva, Sky Sports reported.
However, there was no place for Chelsea striker Morata, with Isco, Marco Asensio, Lucas Vazquez, Rodrigo and Diego Costa preferred in attack.
Morata has struggled for fitness and form since joining the Blues from Real Madrid last summer, and has scored 11 goals in the Premier League since arriving in England.
Meanwhile, Andres Iniesta has been included in the squad the day after playing his final game for Barcelona.
"We've taken the players we feel are the best and feel that we have the ingredients to challenge for the title and are just anxious for things to start now," said Lopetegui.
"We feel that each one will bring his style and personality to the team and this is important for each game and each situation."
Spain open their tournament against neighbours Portugal on June 15 before they face Iran and Morocco in their remaining Group B fixtures.
Lopetegui added: "This is the best and most beautiful competition in the world but at the same time the most difficult as you only have three initial games to prove oneself."
Spain squad for 2018 World Cup:
Goalkeepers: David de Gea, Pepe Reina, Kepa Arrizabalaga
Defenders: Dani Carvajal, Alvaro Odriozola, Gerard Piqué, Sergio Ramos, Nacho, Cesar Azpilicueta, Jordi Alba, Nacho Monreal
Midfielders: Sergio Busquets, Saul, Koke, Thiago Alcantara, Andres Iniesta, David SilvaForwards: Isco, Marco Asensio, Lucas Vazquez, Iago Aspas, Rodrigo, Diego Costa