Barcelona star Xavi has been ruled out of Spain's friendly with Uruguay on Wednesday night with hamstring discomfort.
Real Madrid midfielder Xabi Alonso had already pulled out of the international clash with a groin problem after his club's 1-0 loss to Granada in La Liga on Saturday night.
Alonso's fellow Spain team-mate but La Liga adversary Xavi was examined by a Roja doctor on Sunday after complaining of pain in his right leg, and has been pulled out of the friendly squad to face the Copa America champions.
It is believed that the 33-year-old Barca player picked up the issue in their 1-1 draw with Valencia at the Mestalla on Sunday evening.
Vicente del Bosque still has a very strong squad to choose a starting line-up from, including the likes of Andres Iniesta, Juan Mata and Sergio Ramos.
No replacement has, as of yet, been announced to fill in for Xavi.