Fresh from the Supercoppa Italiana triumph, Sergio Conceicao makes his Serie A debut as Milan coach with Rafael Leao and Alvaro Morata hosting Cagliari.
It kicks off at the Stadio Giuseppe Meazza, also known as San Siro, at 19.45 GMT.
You can follow all the build-up and action as it happens from today's four Serie A games on the Liveblog.
The Rossoneri sacked Paulo Fonseca on December 30 and brought in Conceicao, who made an extraordinary impact with two comeback wins over Juventus and Inter in Riyadh to lift the Supercoppa Italiana trophy.
Now he has to turn Milan's Serie A form around too after one win from the last four, but the injury crisis drags on.
Ruben Loftus-Cheek suffered another muscular issue, joining Alessandro Florenzi and Samuel Chukwueze on the treatment table.
Emerson Royal is also suspended and Noah Okafor transfer-listed, but the good news is that Rafael Leao is finally available for his first start under Conceicao, having come off the bench to inspire the 3-2 victory over Inter.
Cagliari saw their run of four consecutive Serie A defeats ended by the morale-boosting 2-1 win away to rock bottom Monza.
It came at a cost, as Yerry Mina and Zito Luvumbo are out injured, so Jose Luis Palomino steps into defence.
Roberto Piccoli is the centre-forward and top scorer with six goals and three assists in 22 competitive games this season.
Elia Caprile is thrown straight into the starting XI after his transfer from Napoli.
When these teams met in November, it was a 3-3 thriller in Sardinia.
Milan: Maignan; Calabria, Thiaw, Tomori, Theo Hernandez; Musah, Fofana, Reijnders; Pulisic, Morata, Leao
Cagliari: Caprile; Zappa, Palomino, Luperto, Obert; Makoumbou, Adopo; Zortea, Viola, Felici; Piccoli