Ronaldo, the Seleccao captain, has been struggling with a thigh problem this week and was expected to be rested for the World Cup warm-up clash, while his Real Madrid team-mate is yet to recover fully from the calf injury which saw him miss the latter part of the club season, including the Champions League final.
"Ronaldo will be with us but he will not compete," head coach Paulo Bento told reporters on Friday. "Neither will Pepe.
Bento added that the Portugal camp "have no deadlines" on Ronaldo's possible return but stressed the well-being of the player himself was paramount.
"The main thing is the physical health and well-being of the player," he added. "A player is first and foremost a human being.
"That is our main concern and we won't set a time-limit on his return to action."
Portugal face Mexico and Republic of Ireland on June 7 and 10 respectively prior to their World Cup curtain-raiser against Germany.