Milan hope Goncalo Ramos, Christian Pulisic, Diego Moreira and Luka Modric can get them back on track in Serie A, while Atalanta rely on Charles De Ketelaere and Jonathan Rowe.
It kicks off at San Siro at 17.00 UK time (18.00 CEST).
Both these teams are fresh from Europa League victories on Thursday evening that boosted morale, albeit with injuries continuing to pile up.
Milan crushed RB Salzburg 4-0 in Austria thanks to a hat-trick from teenage sensation Alphadjo Cisse, but he is rested here, as Goncalo Ramos, Samuel Chukwueze and Christian Pulisic come in.
Diego Moreira, Luka Modric and Mario Gila also all return after being rested midweek, but Matteo Gabbia and Alexis Saelemaekers are long-term absentees.
It remains to be seen if this is a three-man defence or a 4-3-3 formation.
Atalanta had a disastrous run of three straight defeats, but morale was boosted by the 3-1 win over Venezia and Thursday’s 3-1 victory against Pafos in the Conference League.
Eljif Elmas was sent off against Venezia and is therefore suspended here, with Giacomo Raspadori picking up a fresh muscular injury midweek.
He joins Franck Kessie, Giorgio Scalvini, Odilon Kossounou, Isak Hien and Kamaldeen Sulemana on the treatment table, but Raoul Bellanova shakes off a knock to start.
This will always be a special fixture for De Ketelaere, who was an expensive flop at Milan only to prove what he could do in Bergamo.
Nikola Krstovic takes the centre-forward role from Gianluca Scamacca, with Rowe also stepping back into the starting XI.
Milan vs. Atalanta line-ups
Milan: Maignan; Gila, De Winter, Pavlovic, Moreira; Musah, Modric, Rabiot; Chukwueze, Goncalo Ramos, Pulisic
Atalanta: Carnesecchi; Bellanova, Kristensen, Kolasinac, Bernasconi; Pasalic, Ederson; De Ketelaere, Samardzic, Rowe; Krstovic
