Milan are in a full-blown crisis and look to Charles De Ketelaere, Rade Krunic and Olivier Giroud to turn things around against Domenico Berardi’s equally troubled Sassuolo, but surprisingly drop Rafael Leao to the bench.
It kicks off at the Stadio Giuseppe Meazza at 11.30 GMT.
The Rossoneri are in perhaps the toughest moment of Stefano Pioli’s time at the club, crashing out of the Coppa Italia to 10-man Torino, losing the Supercoppa Italiana 3-0 to rivals Inter and scraping two points from their last three Serie A games.
Things came to a head with the humiliating 4-0 defeat at Lazio and more problems piled on with Fikayo Tomori’s injury and Ismael Bennacer’s ban.
With Fode Ballo-Toure, Mike Maignan, Zlatan Ibrahimovic and Alessandro Florenzi also out of action, joined at the last minute by Sergino Dest, but at least Theo Hernandez and Davide Calabria have shaken off knocks to start.
Rade Krunic is preferred to Tommaso Pobega in midfield, with De Ketelaere and Alexis Saelemaekers stepping in for Brahim Diaz and Junior Messias.
The big shock is that Rafael Leao is dropped to the bench in favour of Ante Rebic, while Matteo Gabbia is preferred to Simon Kjaer at the back.
Sassuolo are in no better condition, hovering above the relegation zone after a shocking run of just two points from eight Serie A games.
They stopped the rot with a 1-1 at Monza, but Andrea Pinamonti is still out of action, with Berardi and Hamed Junior Traore struggling to get over injury issues.
At least Andrea Consigli returns in goal.
Milan: Tatarusanu; Calabria, Gabbia, Kalulu, Theo Hernandez; Krunic, Tonali; Saelemaekers, De Ketelaere, Rebic; Giroud
Sassuolo: Consigli; Marchizza, Erlic, Tressoldi, Rogerio; Frattesi, Obiang, Traore; Berardi, Defrel, Laurienté