Carles Puyol is set to win his 100th cap for Spain in Wednesday's friendly against Uruguay in Qatar, while Vicente Del Bosque will equal the record for most games as Spanish coach.
Chelsea's Cesar Azpilicueta, Malaga's Isco and Mario Suarez of Atletico Madrid could all make their debuts in the game against the reigning South American champions at Doha's Khalifa International Stadium.
Victor Valdes should replace Iker Casillas in goal for Spain, and Puyol stand in as captain as he joins Casillas, Xavi Hernandez, Xabi Alonso, Fernando Torres, Andoni Zubizarreta and Raul Gonzalez in La Roja's 100 cap club.
And Del Bosque believes it is fitting to see Puyol reach the historic mark.
"We are happy that Carles comes into this club," he said. "He has been an example both on and off the field. He deserves it for what he has done, not just his words, but his acts."
Puyol is one of nine Barcelona players in Del Bosque's squad for the game, while Real Madrid have just two, with Alonso also absent. Del Bosque, a former Madrid player and coach, says his club allegiance has always been clear, but never influenced his selection decisions.
"I am a madridista and I have never hidden that," he said. "Barca has the biggest number of players because the national team is a reflection of the clubs. But there are players from many teams. The mixture of all marks the style of the team and the image of Spain."
The game will see World Cup 2010 and Euro 2012 winner Del Bosque equal the record of 68 games as national coach set by Hungarian-born former Spain boss Ladislao Kubala - in a 2-1 loss to England at the 1980 European Championship finals.
Kubala had given Del Bosque his senior debut in 1975, but did not bring him to the 1978 World Cup or use him in that final game in Naples, which turned out to be the former Madrid midfielder's last involvement as a player with the national squad.
"[The record] is something which was unthinkable for me, but I want to say that what Kubala did gets more merit," Del Bosque said. "In his time we played much fewer games each year. We played 16 games in 2012. He was coach for a decade. I never had a problem with Kubala, for leaving me out of the World Cup. He did what he thought was best. Above all, he was a gentleman, very human, which is important for a national coach. He loved football a lot."