Chelsea forward Juan Mata is among the inclusions for Spain’s marathon journey to Panama for an international friendly on Wednesday.
The world and European champions have also recalled Barcelona defender Martin Montoya and Real Betis midfielder Benat, while Athletic Bilbao winger Markel Susaeta is in line to make his international debut.
Montoya is one of eight Barca players in the squad, though playmaker Xavi has been rested along with Real Madrid midfielder Xabi Alonso.
Spain, unbeaten in their past 16 games in all competitions, are on top of Group A in European World Cup qualifying with two wins and a draw from their opening three fixtures.
Their campaign continues at home to Finland on March 22, before taking on France in Paris four days later.
Spain are visiting Panama for the first time on the back of trips to former colonies including Venezuela, Puerto Rico and Costa Rica.
“The trip to Panama is part of a commitment by our country with other Spanish-speaking nations and, in sporting terms, allows us to prepare for upcoming matches,” coach Vicente del Bosque said.
While Panama are 45 places below Spain in the FIFA rankings, the Central American side are expected to provide tough opposition.
Panama have reached the fourth and final round of the CONCACAF World Cup qualifying competition, where they will face the likes of Mexico, the United States and Honduras for one of three automatic berths at Brazil 2014.
Their campaign resumes at home to Costa Rica on February 6, before travelling to Jamaica on March 22.