Kvicha Kvaratskhelia did not train with his Napoli teammates, while Jens Cajuste and Mario Rui are also major doubts for the Champions League decider with SC Braga.
It kicks off at the Stadio Diego Armando Maradona on Tuesday at 20.00 GMT.
In order to guarantee their place in the Round of 16 as runners-up behind Real Madrid, it will be enough for the Partenopei to avoid defeat against Braga.
There are a few problems for coach Walter Mazzarri to deal with, because Kvaratskhelia is suffering from flu symptoms.
He did not train with the squad today, instead only having a brief session by himself in the gym.
Mario Rui is still out of action too, while Cajuste was diagnosed with a knee sprain after the 1-0 defeat to Juventus on Friday evening.
Left-back Mathias Olivera is out until 2024 with a knee injury, so it is likely that Natan will again be used on that side of the defence.