Vicente del Bosque has handed call-ups to the star men from La Roja's European Under-21 Championship-winning side
Thiago Alcantara is one of five Under-21 internationals named in Spain's squad to face Ecuador on Wednesday.
The Bayern Munich man is joined by Inigo Martinez, Koke, Isco and Cristian Tello in the senior setup - with the quintet all part of the side that was victorious at the recent Under-21 European Championship.
Ecuador is Spain's first opponents since losing the final of the Confederations Cup to Brazil in June and Vicente del Bosque has decided to use the opportunity to have a look at his future options.
Atletico Madrid midfielder Koke, Real Sociedad's Martinez and Barcelona's Tello will all meet up with the national team for the first time, while Isco and Thiago will collect their second and fourth caps respectively if selected.
Tello signed an extended contract at Camp Nou last week and was delighted to be selected.
He told Sport : "I'm the happiest man in the world. Not only I have renewed (with Barca), but I have also been summoned to the (Spain) senior team. For me it is a dream come true. I've been my whole life waiting for this moment.
"I've heard while on my way to training through the Twitter of the Spanish Federation. It has been a great surprise."
There is no place in the squad for Manchester United's David de Gea, Barcelona midfielder Xavi or Atletico Madrid striker David Villa.
Full Spain squad:
|Iker Casillas||Real Madrid|
|Alvaro Arbeloa||Real Madrid|
|Inigo Martinez||Real Sociedad|
|Sergio Ramos||Real Madrid|
|Javi Martinez||Bayern Munich|
|Thiago Alcantara||Bayern Munich|
|David Silva||Manchester City|
|Jesus Navas||Manchester City|
|Alvaro Negredo||Manchester City|