Spain coach Vicente Del Bosque could be set to hand debuts to Juan Mata and Fernando Llorente after including the duo in his 20-man squad to face Chile on November 19 at El Madrigal.
Valencia winger Mata, 20, has been a revelation at the Mestalla this season, notching five goals in 14 appearances so far this season.
The 23-year-old Llorente has also been in impressive form for his club, Athletic Bilbao, despite only finding the net twice in 10 games.
Their inclusion comes at the expense of Andoni Iraola and Diego Capel, while Fernando Navarro was also dropped after being in the 21-man squad named for last month's World Cup qualifiers against Estonia and Belgium.
Liverpool's Albert Riera, who was a late inclusion last time out, keeps his place in the squad due to the injury to Barcelona midfielder Andres Iniesta.
There was also no place for Iniesta's 18-year-old team-mate Bojan Krkic who, having made his international debut against Armenia in September, has since returned to the Under-21s.
Liverpool striker Fernando Torres also gets a call-up, despite only recently returning from a hamstring injury he picked up against Belgium.
Spain squad: Iker Casillas (Real Madrid), Jose Manuel Reina (Liverpool); Raul Albiol (Valencia), Alvaro Arbeloa (Liverpool), Joan Capdevila (Villarreal), Juanito (Real Betis), Carlos Marchena (Valencia), Carles Puyol (Barcelona), Sergio Ramos (Real Madrid); Xabi Alonso (Liverpool), Santi Cazorla (Villarreal), Cesc Fabregas (Arsenal), Xavi Hernandez (Barcelona), Juan Mata (Valencia), Albert Riera (Liverpool), Marcos Senna (Villarreal); Dani Guiza (Fenerbache), Fernando Llorente (Athletic Club), Fernando Torres (Liverpool), David Villa (Valencia).