The defender, a commanding presence at the back in all five of his team's games, missed training on Monday after complaining of muscular pain in his thigh and trained separately from the rest of the squad on Tuesday morning.
"You are going to have a sleepless night," coach Fernando Santos told reporters when asked if Pepe would be ready.
"There is a chance he can play tomorrow but we have a very difficult match so all the players have to be 100 percent fit before they can be allowed to play. Tomorrow morning we will have to make the final decision.
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"It's not a new situation for us, we have had situations before other games where players have been in doubt because of injury."
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