Fernando Santos has confirmed that Pepe will miss Portugal's Euro 2016 qualifier against Serbia on Sunday with 'minor trauma'.
The Real Madrid defender worked in the gym on Tuesday and Wednesday and trained outdoors on Thursday, when he completed running and stretching exercises, but pulled out of Friday's session.
"Pepe's a fantastic professional who's worked hard all week to recover from minor trauma," the Coach said at a Press conference.
"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]."
Although there has been no official diagnosis of Pepe's injury, the Portuguese media believe the 32-year-old picked up a thigh injury, given that he emerged unscathed from the Clasico last weekend.
Portugal can topple Group I leaders Denmark with a victory over the Serbians, who were docked three points last October for the chaos which erupted in their match against Albania.