One swap for the Selecao will be enforced due to the unavailability of Rafael Leao, who picked up his second caution of the tournament during the 3-0 demolition of Turkey last time out.
As the AC Milan watches on and recovers ahead of the knockout stages, one of Portugal's fringe attackers will be given the opportunity to start on the left flank, with that honour likely to be handed to either Barcelona's Joao Felix or Wolverhampton Wanderers talisman Pedro Neto.
Porto's Diogo Costa is set to retain his spot in between the sticks but there could be changes in the defence in front of him, with Nuno Mendes dropping out of the side to make room for Nelson Semedo, who would then take Joao Cancelo's position at right-back.
After removing his shirt in celebration of an added-time winner against the Czech Republic last week, Francisco Conceicao is one yellow card away from being suspended for the knockout stages, as too is Fulham enforcer Joao Palhinha, who has cemented himself as a vital cog in Roberto Martinez's XI alongside Vitinha.
At 39 years of age, Cristiano Ronaldo is in line to make his 50th appearance at a major tournament for the Selecao if selected on Wednesday, however the Group F winners could opt to rest their star man and give Goncalo Ramos the nod up front.
The city of Manchester is set to be heavily featured for Portugal in attacking areas, with Manchester United's Bruno Fernandes and Manchester City's Bernardo Silva expected to start after both finding the net against Turkey on the weekend.
Portugal possible starting lineup: Costa; Semedo, A Silva, Dias, Cancelo; Neves, Palhinha, B Silva, Fernandes, Felix; Ronaldo