Gerard Pique, Juan Mata and Fernando Torres were all omitted, while a number of retirements and injuries have left la Roja with a much-changed squadSergio Ramos called upon Spain's new generation to recover from their post-World Cup malaise, starting with Thursday's clash against France.
La Roja dominated international football between 2008 and 2012, winning two European Championships as well as the World Cup in South Africa in 2010.
However, Vicente del Bosque's men failed spectacularly to defend their crown in Brazil, crashing out at the group stage following defeats to Netherlands and Chile.
After their exit, many believed that Spain's possession-based tiki-taka style had been shown up as outdated, with a greater emphasis now on pacy, counterattacking play.
With the midfield duo of Xavi and Xabi Alonso since announcing their international retirement, Ramos believes it is time for the next generation to step up to the mark and prove their worth.
"Both Xavi and Xabi Alonso were important to the team, fundamental in the years of success, but we must not forget there's a new generation with great enthusiasm and quality," he said.
"I don't think there's a theme of a change. The national team has always had its identity and that shouldn't change even if players have left the team.
"We are here to help the new players adapt in the best way but in the end we all go to do things right."
Spain will also be without Andres Iniesta for the friendly in Paris, as it was announced on Monday the Barcelona man had withdrawn with a knee injury, also ruling him out of the Euro 2016 qualifier with Macedonia next Monday.
Contrary to their visitors, France defied many people's expectations by reaching the quarter-finals in Brazil, before losing out 1-0 to eventual winners Germany.
Thursday's clash at the Stade de France represents their first action since then and head coach Didier Deschamps believes his starting XI could be very similar to that which tasted defeat at the Maracana.
"I have not yet seen how everyone is between those who have been playing and those who haven't," he said.
"We have two matches very close together but the team which starts on Thursday will be close to that which started against Germany."
Deschamps will have to contend without Arsenal defender Laurent Koscielny, forced to withdraw after a clash of heads with Leicester City's Jeffrey Schlupp on Sunday. Koscielny has been replaced by Jeremy Mathieu of Barcelona.
Thursday's game marks the first of many international friendlies for France as they build up to hosting the Euro 2016 finals.