Milan revamp with Alexis Saelemaekers in for Rafael Leao alongside Olivier Giroud and Charles De Ketelaere, while Napoli look to Giacomo Raspadori and Kvicha Kvaratskhelia in this Scudetto showdown.
It kicks off at San Siro at 19.45 UK time (18.45 GMT).
These teams went into the weekend as joint Serie A leaders along with Atalanta, so this was a real Scudetto head-to-head.
Both were also missing key players, as the Rossoneri have Rafael Leao suspended, plus Divock Origi, Ante Rebic, Alessandro Florenzi and Zlatan Ibrahimovic injured.
Rather than change system, Stefano Pioli instead uses Saelemaekers on the left side of the attacking trio with De Ketelaere, Rade Krunic and Giroud.
Napoli have Victor Osimhen and Diego Demme injured, while coach Luciano Spalletti must sit in the stands due to a touchline ban.
Raspadori gets the nod rather than Giovanni Simeone in attack, supported by Kvaratskhelia and Matteo Politano.
Milan: Maignan; Calabria, Kjaer, Tomori, Theo Hernandez; Tonali, Bennacer; Saelemaekers, De Ketelaere, Krunic; Giroud
Napoli: Meret; Di Lorenzo, Rrahmani, Kim Min-jae, Mario Rui; Anguissa, Lobotka, Zielinski; Politano, Raspadori, Kvaratskhelia