The Brazilian limped off in the win over Leeds last time out – weeks after having an operation on his left thigh.
And now the 32-year-old, who has been blighted by issues since his arrival from French club Lyon last summer, faces another spell on the sidelines as he needs surgery on his right thigh.
“Marcal, in the last game, had to go out. He had the proper exams, and he has an injury on his right adductor,” said Nuno.
“He’s going to have surgery, so he’ll be out for a couple of weeks.
“The circumstances have been unfortunate. He’s a very good player and all the moments he has been available, he’s been a big help for the team.
“Every time you don’t have a player, you have a problem. When you have a problem, you find a solution.
“Now it’s important to recover well, everything goes well with the surgery, so he can be available for, hopefully, even this season.”
Marcal again joins Willy Boly and Daniel Podence on the sidelines.
On those pair, Nuno – whose side are heading to Newcastle – said: “They are getting better, but they will not be available for this game.
“At this moment, we don’t have a time schedule. It’s all about first taking care of their injuries, and then progressing on the levels of fitness.
“As soon as we consider they are able to play and go on the squad, we will do so.
“But for now there is no schedule. We cannot predict.”
Nuno added on the St James’ Park test: “I’ve seen improvement and we want to achieve that consistency in all moments of the game.
“Our challenge is to sustain this intensity and aggression, with and without the ball, and improve our game.”