Santos's side head into the exhibition match on the back of a nail-biting 2-1 World Cup qualifying win over the Republic of Ireland, during which Cristiano Ronaldo's heroics saw him surpass Ali Daei as the highest men's international goalscorer of all time.
However, Ronaldo has now left the camp after his booking ruled him out of their battle with Azerbaijan next week, while Andre Silva and the uncapped Otavio are in line to replace Diogo Jota and Rafa Silva in the final third.
Wolverhampton Wanderers' Francisco Trincao has been called up as a replacement for the injured Pedro Goncalves and should also earn some minutes, while Goncalo Guedes could start on the left following Ronaldo's departure.
A new-look midfield could see club teammates Ruben Neves and Joao Moutinho pair up in place of Bernardo Silva and Bruno Fernandes, while Danilo Pereira could displace Joao Palhinha in the number '6' role as Santos looks ahead to next week's qualifier with Azerbaijan.
Portugal possible starting lineup: Costa; Semedo, Duarte, Dias, Mendes; Pereira, Neves, Moutinho; Otavio, A. Silva, Guedes