Brazil-born Pepe, who cost Real Madrid 30 million euros from Porto in 2007, damaged knee ligaments in December and has not played since.
Portugal coach Carlos Queiroz produced several surprises with Deportivo Coruna central defender Ze Castro called up even though he did not feature in the squad for any of the qualifiers.
"Of course, it's a surprise as this year I hadn't been called up consistently... I would have had more hopes if the season had gone like I thought it could have, I had plenty of physical problems but now I am at my best," Castro told the SportTV channel.
Queiroz called up four other central defenders, including a surprise selection for Lille's Ricardo Costa.
"When I played for the national side against Estonia, I played as a sweeper, and the coach knows I can play in that position," the 27 year-old Castro added.
Queiroz also included two goalkeepers with little international experience, Porto's Beto and Iraklis' Daniel Fernandes keeping Benfica's Quim and Chelsea's Hilario out.
In midfield, Sporting's Joao Moutinho, who played in five qualifiers but had a low-key season, was the main omission.
His club mate Yannick Djalo was left out of Portugal's frontline, with Queiroz calling up Zenit forward Danny who has returned to form after a knee injury.
