The Primeira Liga leader goes into its final Group B match at Estadio do Dragao in second place, with Atleti and Milan also in the hunt to qualify for the last 16 behind runaway leader Liverpool.
Porto will have to do without veteran centre-back Pepe, while Marko Grujic is a doubt due to an ankle injury.
Coach Sergio Conceicao said during a news conference on Monday: "Pepe tested positive for COVID. It's an uncontrollable situation, it's part of society.
"As for Grujic, two days ago in training, with the poor quality of our pitches, he sprained [his ankle] and is in doubt."
Milan and Atleti are just a point behind Porto and Jurgen Klopp will ring the changes for Liverpool's trip to San Siro.
Conceicao believes it should already have been mission accomplished for his side, who must win to make certain of a place in the knockouts.
He said: "In this circumstance, in the last round of the group stage [to be in contention to progress] is something my team deserves praise for, and it would be deserved to be already in the round of 16.
"Any of the teams [Porto, Milan and Atleti] can dream of going through, but we have to focus on what we have to do in the game and win it."
Mateus Uribe (suspended) and Ivan Marcano (foot) are also ruled out, while Francisco Conceicao (hip) and Joao Mario (fatigue) are rated as doubtful.