Juan Mata has been rewarded for his fine form for Manchester United with a recall to the Spain squad.
Mata was on Thursday named United's player of the month for October, narrowly edging out Ander Herrera, who was also included by Spain boss Julen Lopetegui for the World Cup qualifier with Macedonia and friendly against England at Wembley.
Sergio Escudero has earned his first senior call-up after impressing for Jorge Sampaoli's Sevilla, while Borussia Dortmund's Marc Bartra is included in the absence of injured trio Gerard Pique, Sergio Ramos and Javi Martinez.
Andres Iniesta and Jordi Alba also miss out on the 25-man squad through injury, as does Santi Cazorla. Meanwhile, Chelsea duo Cesc Fabregas and Pedro have been overlooked along with club team-mate Marcos Alonso, who had been tipped for a place.
Aritz Aduriz returns after scoring five goals for Athletic Bilbao in their Europa League win over Genk on Thursday.
"We have a lot of absences and we can't stop to mourn them," said Lopetegui, whose side meet Macedonia on November 12 and England three days later. "They are what they are and we can't change them.
"Some of the players are certainties but we have questions about how they will compete. The second game is a friendly and it allows us to make other decisions, especially if we need to cover any possible casualties."
Asked about the return of 35-year-old Aduriz, Lopetegui suggested that fellow veterans including Iker Casillas and David Villa could yet earn a comeback.
"There is no problem if a player is of one age or another," he said. "Villa is in another league and he's at a good level. He's competitive and making a difference, but we have the three strikers.
"I will not close the door to anyone. We'll make decisions based on what we see and how we feel."
Spain squad in full:
Goalkeepers: Pepe Reina (Napoli), David De Gea (Manchester United), Sergio Asenjo (Villarreal).
Defenders: Nacho (Real Madrid). Marc Bartra (Borussia Dortmund), Inigo Martinez (Real Sociedad), Cesar Azpilicueta (Chelsea), Nacho Monreal (Arsenal), Dani Carvajal (Real Madrid), Sergio Escudero (Sevilla), Sergi Roberto (Barcelona).
Midfielders: Ander Herrera (Manchester United), Sergio Busquets (Barcelona), Koke (Atletico Madrid), Isco (Real Madrid), Thiago (Bayern Munich), David Silva (Manchester City), Juan Mata (Manchester United), Lucas Vazquez (Real Madrid), Jose Callejon (Napoli), Vitolo (Sevilla).
Forwards: Alvaro Morata (Real Madrid), Diego Costa (Chelsea), Nolito (Manchester City), Aritz Aduriz (Athletic Bilbao).