Giacomo Raspadori is the favourite to lead the Napoli attack against Milan rather than Giovanni Simeone, while Hirving Lozano is available again.
It kicks off on Sunday at San Siro at 19.45 UK time (18.45 GMT).
The Partenopei are missing injured Victor Osimhen and Diego Demme, so coach Luciano Spalletti has to pick his centre-forward.
He chose Simeone for the midweek Champions League victory away to Glasgow Rangers, but Raspadori is tipped to take the reins of their attack tomorrow evening.
The 22-year-old has found the net in each of his last two games, a late winner against Spezia in Serie A and coming off the bench to complete the 3-0 rout at Ibrox.
Raspadori also has history here, scoring both goals when Sassuolo came away with a 2-1 victory at San Siro in April 2021.
He also contributed an assist when Sassuolo won here 3-1 last season, so won both matches he played at the Stadio Giuseppe Meazza.
While Lozano is available after recovering from flu and a knock to the head, he is not expected to start, with Matteo Politano and Kvicha Kvaratskhelia on the flanks.
Napoli (probable): Meret; Di Lorenzo, Rrahmani, Kim Min-jae, Mario Rui; Anguissa, Lobotka, Zielinski; Politano, Raspadori, Kvaratskhelia