Atalanta want to make up for the Old Trafford turnaround with Duvan Zapata and Josip Ilicic starting, but the injury crisis remains in defence, while Cristiano Ronaldo leads Manchester United.
It kicks off at 20.00 GMT at the Gewiss Stadium in Bergamo.
Champions League liveblog: Atalanta vs. Man United and Juventus vs. Zenit
La Dea had been 2-0 up at Old Trafford last time before capitulating 3-2 after the break with Ronaldo’s late towering header.
This is Ronaldo’s first return to Italian soil since leaving Juventus over the summer and he already beat Atalanta in the Coppa Italia Final back in May.
Gian Piero Gasperini’s injury crisis drags on, missing Rafael Toloi, Robin Gosens, Hans Hateboer and Matteo Pessina.
Berat Djimsiti and Merih Demiral are not 100 per cent fit, but start anyway with Marten de Roon again a makeshift defender, while Mario Pasalic supports Ilicic and Duvan Zapata.
Manchester United make the trip without Viktor Lindelof, but switch to a 3-5-2 formation to better neutralise Atalanta’s tactics after impressing against Spurs.
Fresh from a 3-0 win over Tottenham, but with Ole Gunnar Solskjaer still at risk, Paul Pogba steps into the midfield with Bruno Fernandes supporting CR7.
Atalanta: Musso; De Roon, Demiral, Palomino; Zappacosta, Freuler, Koopmeiners, Maehle; Pasalic; Ilicic, Duvan Zapata
Atalanta bench: Rossi, Sportiello, Muriel, Pezzella, Malinovskyi, Djimsiti, Scalvini, Miranchuk, Lovato, Piccoli
Manchester United: De Gea; Bailly, Varane, Maguire; Wan-Bissaka, Bruno Fernandes, McTominay, Pogba, Shaw; Cristiano Ronaldo, Rashford
Manchester United bench: Henderson, Alex Telles, Dalot, Fred, Lingard, Mata, Matic, Van de Beek, Cavani, Greenwood, Martial, Sancho
Ref: Vincic (SVN)