Milan are forced to do without several key players at San Siro, while Juventus have some doubts in attack for the San Siro showdown.
It kicks off on Sunday at 19.45 UK time (18.45 GMT).
Inter beat Torino 3-0 to temporarily recapture top spot, putting even more pressure on the Rossoneri and third-place Bianconeri.
Both teams have numerous issues to deal with that rather limit their options.
Mike Maignan and Theo Hernandez are both suspended, while Marco Sportiello is also injured, so Stefano Pioli is forced to look to his third-choice goalkeeper Antonio Mirante.
Samuel Chukwueze picked up an injury on international duty and is out for a month, while Ruben Loftus-Cheek has not fully recovered either, joining Ismael Bennacer and Mattia Caldara on the treatment table.
Pierre Kalulu and Rade Krunic are back in the squad after several weeks out, but probably not fit to start, so Alessandro Florenzi will be in left-back, with Yunus Musah and Yacine Adli probably joining Tijjani Reijnders in midfield, though Tommaso Pobega is also an option.
Juventus have problems too, as Danilo, Alex Sandro and Mattia De Sciglio are injured, with Paul Pogba suspended for failing a doping test and Nicolò Fagioli beginning his ban for illegal betting.
Federico Chiesa and Dusan Vlahovic are available, but the Italian is certainly not fit to start, while the Serbian is not at his best either.
Arkadiusz Milik will start, with either Vlahovic or Moise Kean in support.
There are suggestions Max Allegri could move to a 4-4-2 formation with Timothy Weah and Andrea Cambiaso as full-backs.
Otherwise, the 3-5-2 remains with Daniele Rugani filling in the defence.
Probable line-ups
Milan (4-3-3): Mirante; Calabria, Thiaw, Tomori, Florenzi; Musah, Adli, Reijnders; Pulisic, Leao, Giroud
Juventus (3-5-2): Szczesny; Gatti, Bremer, Rugani; Weah, McKennie, Locatelli, Rabiot, Kostic; Milik, Vlahovic