Sergio Ramos and Juanfran have pulled out of the Spain squad for the forthcoming international friendlies with England and Belgium.
Ramos dislocated his shoulder in Real Madrid's 4-0 Champions League win over Shakhtar Donetsk in September and missed Spain's last two Euro 2016 qualifiers.
He aggravated the joint on Sunday in the act of scoring against Sevilla and was withdrawn after 32 minutes as Rafa Benitez's side suffered a 3-2 defeat at the Estadio Ramón Sánchez-Pizjuán.
Ramos will instead focus his attention on recovering in time for Madrid's Clasico clash with Barcelona on November 21.
"The shoulder is not good. In scoring the goal I have fallen on my arm," he said.
"The priority must be to recover as soon as possible. I played four or five games with an injection but have had a relapse again."
Juanfran will also be absent after sustaining a thigh injury in Atletico Madrid's 1-0 win over Sporting Gijon on Sunday.
Real defender Nacho and Athletic Bilbao's Oscar de Marcos have been selected as the replacements for the duo.