Alexis Sanchez, Marcus Thuram and Davide Frattesi are among the changes as Inter visit RB Salzburg, knowing a win would guarantee Round of 16 qualification.
It kicks off at the Red Bull Arena at 20.00 GMT.
The Nerazzurri have had a very strong campaign so far, sitting top of Serie A and with seven points from three Champions League fixtures.
However, RB Salzburg are third and could get back into contention, so this is a crucial game.
Denzel Dumfries is rested after not taking part in yesterday’s training session, while Benjamin Pavard and Juan Cuadrado are injured, plus Marko Arnautovic returns to the bench after more than a month out with a thigh strain.
Lautaro Martinez is also among those given the night off, as Simone Inzaghi rotates with Carlos Augusto, Matteo Darmian, Frattesi and Yann Bisseck.
RB Salzburg have a lengthy absentee list, including Maurits Kjaergaard (who is going to have shoulder surgery), Sekou Koita, Bryan Okoh, Justin Omoregie, Kamil Piatkowski, Lukas Wallner, Aleksa Terzic and Dijon Kameri.
Fernando is only fit for the bench and centre-back Omar Soulet is out, so Samson Baidoo and Luka Sucic step in.
Roko Simic is the son of former Inter and Milan defender Dario Simic, so was born in Milan.
It was a tight game at San Siro, the Nerazzurri emerging 2-1 winners thanks to Alexis Sanchez and a Hakan Calhanoglu penalty.
RB Salzburg: Schlager; Dedic, Baidoo, Pavlovic, Ulmer; Sucic, Bidstrup, Capaldo, Gloukh; Simic, Konate
Salzburg bench: Mantl, Krumrey, Fernando, Diambou, Ratjkov, Gourna-Douath, Forson, Morgalla, Nene
Inter: Sommer; Bisseck, Acerbi, Bastoni; Darmian, Frattesi, Calhanoglu, Mkhitaryan, Carlos Augusto; Alexis Sanchez, Thuram
Inter bench: Di Gennaro, Audero, Dumfries, De Vrij, Arnautovic, Martinez, Klaassen, Asllani, Barella, Dimarco, Stabile
Ref: Gozubuyuk (NED)
Player statistic
27' | Yann Bisseck |
49' | Hakan Calhanoglu | |||
Strahinja Pavlovic | 51' | |||
Oscar Gloukh | 75' | |||
85' | Lautaro Martínez |