Pepe misses Portugal’s Euro 2016 semi-final against Wales with Bruno Alves partnering Jose Fonte in central defence.
The Real Madrid centre-back was a major doubt ahead of the match due to a thigh injury and missed training sessions in the build-up to the game.
Following Portugal's victory over Poland in the quarter-final, Fernando Santos has made two other changes to his starting team.
Raphael Guerreiro starts at left-back ahead of Eliseu, while Danilo replaces William Carvalho in central midfield.
For Wales, who are in the semi-finals after a 3-1 win over Belgium in the quarter-finals, James Collins replaces Ben Davies, while Andy King deputises for Aaron Ramsey, who is also suspended.
PORTUGAL: Rui Patricio, Cédric, Bruno Alves, Fonte, Guerreiro, Danilo, A. Silva, Joao Mario, Renato Sanches, Nani, Ronaldo
WALES: Hennessey, Gunter, Chester, A Williams, Collins, Taylor; Allen, Ledley, Bale, King; Robson-Kanu