Milan give Joao Felix his first start for the trip to Lorenzo Colombo’s Empoli, but Rafael Leao and Christian Pulisic are benched.
It kicks off at the Stadio Castellani at 17.00 GMT.
The Rossoneri revamped their squad in the January transfer window and were especially active on deadline day with a slew of moves.
Joao Felix already scored on his debut, from a Santiago Gimenez assist in the 3-1 Coppa Italia quarter-final victory over Roma, and here gets his first start.
Kyle Walker has been a regular since his first appearance in the derby draw with Inter, but Tammy Abraham takes the centre-forward role for now.
Rafael Leao is carrying an ankle issue and is rested ahead of the Champions League play-off with Gimenez’s old club Feyenoord on Wednesday.
It had been reported that Tijjani Reijnders would also be given time off, but instead it is Pulisic on the bench.
The injury list includes Emerson Royal, Ruben Loftus-Cheek, Alessandro Florenzi and new buy Warren Bondo.
Empoli are without a victory since December 8 when thrashing Verona 4-1, managing just two points from their last eight Serie A games.
They were beaten 4-1 by Juventus, but that result did not reflect the performance, falling to pieces after going down to 10 men.
Youssouf Maleh is therefore suspended with a huge absentee list including Tino Anjorin, Ardian Ismajli, Jacopo Fazzini, Ola Solbakken, Nicolas Haas, Tyronne Ebuehi, Saba Sazonov and Pietro Pellegri.
At least Alberto Grassi and Giuseppe Pezzella return from bans, while it is a special game for Milan youth product Colombo and Rossoneri-owned goalkeeper Devis Vasquez.
Empoli vs. Milan line-ups
Empoli: Vasquez; De Sciglio, Marianucci, Viti; Gyasi, Grassi, Henderson, Pezzella; Cacace, Esposito; Colombo
Milan: Maignan; Walker, Tomori, Pavlovic, Theo Hernandez; Musah, Reijnders, Fofana, Jimenez; Joao Felix, Abraham
Player statistic
| 18' |  |
João Félix | ||
| 36' | |
Fikayo Tomori | ||
| Liam Henderson | |
45+3' |
| 55' |  |
Fikayo Tomori | ||
| Alberto Grassi | |
62' | ||
| Luca Marianucci |  |
65' | ||
| 65' | |
Santiago Giménez | ||
| 68' |  |
Rafael Leão (Assist: Christian Pulisic) | ||
| 76' | |
Santiago Giménez (Assist: Christian Pulisic) |
Match statistic
not one italian in the line up