Milan give 16-year-old Francesco Camarda his first Serie A start with Rafael Leao and Christian Pulisic for a tricky trip to Cagliari.
It kicks off at the Unipol Domus at 17.00 GMT.
You can follow all the build-up and action as it happens from this game, Venezia-Parma and Juventus-Torino on the Liveblog.
The Rossoneri are fresh from their remarkable 3-1 Champions League victory away to Real Madrid on Tuesday evening.
However, Alvaro Morata suffered head trauma during an accidental collision with teammate Strahinja Pavlovic in training and is therefore out of action.
With Luka Jovic not fully fit either, plus Matteo Gabbia, Alessandro Florenzi and Ismael Bennacer injured, the first Serie A start goes to 16-year-old Camarda.
He becomes the second youngest player to start in the top flight during the modern era for Milan, just two days shy of Gianluigi Donnarumma’s record.
Rafael Leao also returns after being dropped for three consecutive Serie A matches, with Pulisic in a more central role and Samuel Chukwueze on the right.
Cagliari lost their last three league games on the bounce and the chaotic 2-1 defeat to Lazio saw both Michel Adopo and Yerry Mina sent off, so they are therefore suspended.
Jose Luis Palomino and Alessandro Deiola step in, with Zito Luvumbo and Nicolas Viola supporting Roberto Piccoli.
Another surprise is in goal, where Albania international Alen Sherri gets the gloves.
Milan’s last defeat to the Sardinians was 2-1 in May 2017, followed by 11 wins and two draws in all competition.
Cagliari vs. Milan line-ups
Cagliari: Sherri; Hoe, Palomino, Lupert, Bird; Makoumbou, Deiola; Zortea, Violet, Dream; Small
Milan: Cousins; Emerson Royal, Thiaw, Pavlovic, Theo Hernandez; Fofana, Reijnders; Chukwueze, Pulisic, Leao; Camarda
