Pepe is a doubt for Wednesday's Euro 2016 semi in Lyon as Portugal and Wales go head-to-head for a place in the final.
The defender has been one of Fernando Santos' most consistent performers in France so far, but has picked up a problem with his thigh muscle and did not train on Monday.
However, he did a separate training session with the team's backroom staff on Tuesday, and is facing a race against time to be fit as Portugal look to win their first game of the tournament in 90 minutes.
Pepe will certainly be wanted to help keep his Real Madrid team-mate Gareth Bale at bay and Portugal's Andre Gomes believes they have the right components to tame The Dragons.
"I know Gareth Bale from the Spanish league," said the Valencia midfielder. "I've also played against British teams in the past, so I know their way to play, their style.
"We are preparing to face a very strong Wales team. They attack very well. I think they counter-attack very well as well, but we will use our weapons the best way we can to beat them on Wednesday."
The game also sees two of the world's biggest football stars go toe-to-toe, with Portugal captain Cristiano Ronaldo and Wales' Bale expected to start, although the latter doesn't believe the game should focus on the duo.
"It's not about two players. We know and everybody knows that it's about two nations in the semi-final - 11 men against 11," Bale said.
"[Ronaldo] is a fantastic player, everyone knows what he can do. But we don't worry about the opposition. We just do what we do. It's about how we perform as a team, and as a team we can shut out a lot of threats."
Team news
One Portugal player who is a certain omission is William Carvalho, who misses the game through suspension after picking up two yellow cards.
Gomes missed the quarter-final clash with Poland with his own thigh strain, but is expected to be available to face Wales.
Wales have their own suspension problems, with Aaron Ramsey and Ben Davies sidelined, although manager Chris Coleman remains unfazed by their absence and has told Sky Sports News HQ he is "almost sure" who he will pick in their place.
"Some of Aaron Ramsey's performances have been off the chart and we've noticed the difference in Ben in this last season since he has been at Tottenham and fighting for that left-back spot with Danny Rose," Coleman said.
"But the attitude of the players who haven't played has been fantastic and that has kept the dressing room really strong and kept the vibe really positive.
"The other guys who have worked hard will now get a look in for this next game and it's not a bad one to get a start in the semi-final of a major tournament."
Gareth Bale has taken part in full training after doing separate work on Monday and Dave Edwards also trained apart from the squad on Tuesday.
Opta stats
This will be the fourth encounter between Portugal and Wales, their first since June 2000 when the Portuguese won 3-0 in a friendly.
It's also their first ever competitive encounter, their three previous meetings all being friendlies.
Portugal have reached the semi-finals for the fifth time in seven Euro participations. In fact, since their first European Championship in 1984, only Germany have made the last four on more occasions (six) than Portugal.
However, Portugal have played the most games in the history of the European Championship without ever winning the tournament: 33 games, 0 trophy. Their only Euro final ended in a 1-0 defeat against Greece in 2004.
Portugal are unbeaten in their 12 competitive fixtures under Fernando Santos (W8, D4), all eight of their wins in that run being decided by a single goal.
Wales have already bettered their only previous performance in a major tournament. In the 1958 World Cup, they were knocked out in the quarter-finals by eventual winners Brazil.
Wales have lost only two of their 10 games at major tournaments, both by a one-goal difference: against Brazil in 1958 (0-1) and England in 2016 (1-2).
Only France have scored more goals (11) than Wales (10) at this year's European Championship.
Cristiano Ronaldo has played in more games than any other player in Euro finals (19). He's only one goal short of Michel Platini's record of nine goals in the competition.
Ronaldo has failed to score with any of his 41 direct free-kicks at major tournaments (World Cup and Euros). Meanwhile, his Real Madrid team-mate Gareth Bale has scored with two of the five direct free-kicks he's attempted with Wales at Euro 2016.
Bale has had more shots on target than any other player at Euro 2016 (14). He's scored with three of them.
In the quarter-finals, Renato Sanches became the youngest scorer in the knockout stages of a Euro tournament (18 years and 10 months).
Merson's predictions
Wales have got a few players missing, especially Aaron Ramsey who's been outstanding in the tournament, but I think if Pepe doesn't play for Portugal then it's a major loss. I know people say that he acts up on the pitch but he is a good, good defender and I think he'll be badly missed if he doesn't play.
Portugal haven't won a game yet, not in 90 minutes. I don't fancy them at all, and I think it will show how far Wales have come.
PAUL PREDICTS: Portugal 1-2 Wales in 90 minutes (12/1 with Sky Bet)
Betting
Portugal are Sky Bet's 6/5 favourites for the victory in 90 minutes, with Wales the 13/5 outsiders again while the draw and extra-time is a 2/1 chance. Either side to win during the additional 30 minutes is 13/2 while a penalty shoot-out is a 15/4 chance.
With France and Germany 7/4 joint favourites, Portugal are given a 7/2 chance of lifting the trophy while Chris Coleman's side are 8/1 outsiders. Cristiano Ronaldo heads the first goalscorer betting at 11/4 followed by Gareth Bale at 9/2, while the duo are enhanced from 5/1 to 7/1 to both find the net in Sky Bet's Price Boosts.