Spain coach Vicente del Bosque has rung the changes in his first squad list since their World Cup humiliation, bringing in five uncapped players among eight new faces.
Among those left out of the 23-man squad for the start of their Euro 2016 qualifying campaign are Barcelona defender Gerard Pique, Chelsea striker Fernando Torres and Manchester United playmaker Juan Mata.
Xavi and Xabi Alonso are also missing after announcing their international retirements following the World Cup, while Jose Reina, David Villa and long-term injury victim Javi Martinez make up those omitted.
In their place, Del Bosque has largely gone for youth, calling up uncapped quintet Dani Carvajal, Raul Garcia, Kiko Casilla, Mikel San Jose and Paco Alcacer, while recalling Isco, Marc Bartra and Ander Iturraspe.
Spain are looking to rebuild following their miserable summer showing in Brazil, where they became the first reigning champions ever to be dumped out of the World Cup after losing their opening two matches.
In their Group B opener Del Bosque's side were thrashed 5-1 by Holland - the first time Spain had conceded five goals in an international since 1963 and the biggest losing margin by any defending champion.
They then lost 2-0 to Chile to exit the competition after just six days before finishing up with a 3-0 win over Australia.
The two-time reigning European champions face France in a friendly next Thursday before starting their Euro 2016 qualifying campaign against Macedonia on September 8.
Spain squad: Casillas (Real Madrid), De Gea (Manchester United), Casilla (Espanyol); Ramos (Real Madrid), Carvajal (Real Madrid), Juanfran (Atletico Madrid), San Jose (Athletic Bilbao), Albiol (Napoli), Bartra (Barcelona), Alba (Barcelona), Azpilicueta (Chelsea); Busquets (Barcelona), Cazorla (Arsenal), Fabregas (Chelsea), Iturraspe (Athletic Bilbao), Pedro (Barcelona), Isco (Real Madrid), Silva (Manchester City), Iniesta (Barcelona), Koke (Atletico Madrid), Garcia (Atletico Madrid); Costa (Chelsea), Alcacer (Valencia).