The Milan derby comes amid speculation about Paulo Fonseca's position as the Rossoneri's manager, so the stakes will be particularly high when selecting his starting XI to face the Italian champions.
After being substituted during Tuesday's 3-1 Champions League defeat to Liverpool, goalkeeper Mike Maignan faces a race against time to overcome a knee injury - believed to be bruising - and Fonseca may have to field a 19-year-old rookie if the Frenchman is not passed fit.
Experienced back-up Marco Sportiello has been sidelined for several weeks, so teenager Lorenzo Torriani could be pitched into a must-win derby, having played most of the second half in midweek.
Elsewhere, Milan will be without Ismael Bennacer (ankle), Alessandro Florenzi (ACL) and Malick Thiaw (ankle), but that would not stop Fonseca potentially naming an unchanged XI, notwithstanding Maignan's possible absence.
However, one change could come in defence, where Emerson Royal and Davide Calabria continue to battle it out for the problem right-back position.
Although alternatives such as Noah Okafor, Samu Chukwueze and Tammy Abraham are available, the Rossoneri's attacking triumvirate should again feature Alvaro Morata, Christian Pulisic and Rafael Leao.
The latter has a point to prove this weekend, as across the past 15 derbies he has been on the winning side just three times - losing 10 - while making only five goal contributions.
AC Milan possible starting lineup: Maignan; Emerson, Tomori, Pavlovic, Hernandez; Fofana, Loftus-Cheek; Pulisic, Reijnders, Leao; Morata