Forwards Raul Garcia (Atletico Madrid) and Paco Alcacer (Valencia), along with defender Dani Carvajal (Real Madrid) and goalkeeper Kiko Casilla (Espanyol) are among the fresh names brought into the national squad for their upcoming friendly and Euro 2016 qualifying opener.
After a calamitous World Cup in Brazil, in which the champions failed to make it out of the group stage, Del Bosque has heeded the calls of bringing in new blood - with Garcia, Alcacer, Carvajal and Casilla all uncapped at international level.
Garcia, 28, is the oldest of the quartet, and said he was looking to make the most of his "reward" to be called up for their friendly in Paris on Thursday, and their Euro qualifier in Valencia on Monday.
"Being called up to the Spanish national team is a reward and it comes when it comes. I want to do my job well and everyone has told me this is a fantastic group of people," he said.
"It's always good to get a call to join La Roja. This is a dream every player has from childhood and I must try to make the most of it. I'll work hard and enjoy myself, if I get the opportunity to make my debut."
Shot-stopper Casilla, 27, said he discovered he was required at national level via social media.
"I'm very happy to be here. I want to make the most of this, enjoy myself and to learn. I never expected the call. I've been working hard to perform well in my team and this is a reward for that," Casilla said.
"I was in training at Espanyol and my team-mate, Salva Sevilla, told me that he'd seen it on Twitter and I couldn't quite believe it."
Carvajal, 22, and Alcacer, 21, bring youth to the squad, but no lack of experience - the former playing all 120 minutes for UEFA Champions League winners Real last season.
He said his Spanish Real team-mates advised him on how to approach the call-up.
"It's a huge joy to be here and who doesn't feel excited to be a part of their national team. Iker Casillas and Sergio Ramos told me to enjoy this, because it's always a reward and that's what I intend on doing," Carvajal said.
Alcacer said he was thrilled to make the senior squad, after representing Spain at six different under-age levels.
"I've been working hard during this start to the season with my club, Valencia, so my heart skipped a beat when I received the news I would be in the full national team," Alcacer said.