Milan are forced to revamp and rely on Rafael Leao, Olivier Giroud and Christian Pulisic, while Juventus look to Arkadiusz Milik, Timothy Weah and Moise Kean.
It kicks off at San Siro at 19.45 UK time (18.45 GMT).
You can follow all the build-up and action as it happens on the LIVEBLOG.
This is a Scudetto showdown, as the Rossoneri need a victory to recapture top spot from Inter, while the Bianconeri are in third place.
Both sides have to completely reshuffle due to a lengthy absentee list.
Mike Maignan and Theo Hernandez are suspended, so with Marco Sportiello injured too, Milan have to use their third-choice goalkeeper Antonio Mirante.
Also out of action are Ruben Loftus-Cheek, Samuel Chukwueze, Ismael Bennacer, Mattia Caldara and Davide Bartesaghi, while Pierre Kalulu and Rade Krunic are only fit for the bench.
That means Alessandro Florenzi as a makeshift left-back, with Yacine Adli as the midfield playmaker
Juventus have problems too, as Danilo, Alex Sandro and Mattia De Sciglio are injured, so Daniele Rugani steps into defence.
Although Dusan Vlahovic and Federico Chiesa are in the squad, they are only ready for a spot on the bench, so Moise Kean partners Arkadiusz Milik upfront.
It is the same midfield that won the Derby della Mole against Torino, including Timothy Weah, the son of former Milan legend George.
Juve have not beaten Milan since a 3-1 result here in January 2021, managing just two draws and three defeats, scoring one goal and conceding seven.
Milan: Mirante; Calabria, Thiaw, Tomori, Florenzi; Musah, Adli, Reijnders; Pulisic, Leao, Giroud
Juventus: Szczesny; Gatti, Bremer, Rugani; Weah, McKennie, Locatelli, Rabiot, Kostic; Milik, Kean
Player statistic
Malick Thiaw | 40' |
52' | Timothy Weah | |||
Tijjani Reijnders | 61' | |||
64' | Manuel Locatelli (Assist: Timothy Weah) | |||
67' | Weston McKennie | |||
71' | Federico Gatti | |||
72' | Manuel Locatelli |