Inter are forced to revamp and give Christian Eriksen a rare start behind Romelu Lukaku and Alexis Sanchez against Marcus Thuram’s Borussia Monchengladbach, while Matteo Darmian debuts.
It kicks off at San Siro at 20.00 UK time (19.00 GMT).
Inter are in the same group as Borussia Monchengladbach, Real Madrid and Shakhtar Donetsk.
The Nerazzurri are dealing with the effects of injuries and COVID-19 to cut down the squad at Antonio Conte’s disposal.
Alessandro Bastoni and Radja Nainggolan are only fit for the bench after recovering from Coronavirus, while Milan Skriniar, Ashley Young, Roberto Gagliardini and Ionut Radu are still positive.
Matias Vecino is injured, with Marcelo Brozovic and Stefano Sensi not 100 per cent fit.
Just hours before kick-off, it was announced that Achraf Hakimi had also tested positive, when he had been guaranteed a starting spot.
Therefore, Matteo Darmian is given his Inter debut on the right side of midfield after his deadline day transfer from Parma.
It all means Eriksen is practically forced into the starting XI, but Alexis Sanchez gets the nod rather than Lautaro Martinez as partner to Romelu Lukaku.
Borussia Monchengladbach have a few of their own issues to deal with, missing Denis Zakaria, Laszlo Benes, Andreas Poulsen, Mamadou Doucoure, Louis Beyer, Kaan Kurt and Inter loanee Valentino Lazaro.
Assane Plea was rested at the weekend in a 1-1 draw with Wolfsburg, but is back leading the way with support from Marcus Thuram, Jonas Hofmann and Breel Embolo, who is picked rather than Lars Stindl.
Inter: Handanovic; D'Ambrosio, De Vrij, Kolarov; Darmian, Barella, Vidal, Perisic; Eriksen; Lukaku, Alexis Sanchez
Inter bench: Padelli, Stankovic, Lautaro Martinez, Ranocchia, Boscolo Chio, Moretti, Nainggolan, Squizzato, Brozovic, Bastoni, Pinamonti
Borussia Monchengladbach: Sommer; Lainer, Ginter, Elvedi, Bensebaini; Kramer, Neuhaus; J Hofmann, Embolo, Thuram; Plea
Gladbach bench: Sippel, Grun, M Lang, Herrmann, Wolf, Stindl, Traore, Wendt, Jantschke, Reitz
Ref: Kuipers (NED)