Portugal boss Fernando Santos has revealed that Pepe will miss Sunday's Euro 2016 qualifier against Serbia.
The Real Madrid centre-back joined up with his national team carrying a knock and, despite training earlier in the week, he has been ruled out with a "minor trauma".
"Pepe's a fantastic professional who's worked hard all week to recover from minor trauma," Santos told reporters. "Unfortunately, he doesn't meet all the necessary conditions to play [on Sunday] and will sit out.
"We thought he could play [against Serbia] but we had to make a decision [on Saturday morning]."
Portugal, who failed to make it out of the group stages of the 2014 World Cup, can move to the top of Group I with victory over the Serbians.