Lautaro Martinez and Marcus Thuram lead the way with Benjamin Pavard in defence as Inter seek their first Champions League win against Angel Di Maria’s Benfica.
It kicks off at San Siro at 20.00 UK time (19.00 GMT).
The Nerazzurri opened their European campaign with a late 1-1 draw away to Real Sociedad, snatched by Lautaro Martinez, who also came to their rescue by becoming the first ever Serie A substitute to score four goals in the victory over Salernitana on Saturday.
Davide Frattesi and Marko Arnautovic are out of action, but Juan Cuadrado returns to the bench.
The only major doubt for Simone Inzaghi was between Matteo Darmian and Denzel Dumfries on the right.
Benfica started their group with a surprise 2-0 home defeat to RB Salzburg, but it was largely dictated by the Antonio Silva red card just 13 minutes into the match, which is why he is also suspended today.
It was a disastrous start, as they also gave away a penalty in the third minute, which previous Inter transfer target Anatoliy Trubin saved.
The star man is former Juventus forward Di Maria, who has already scored six goals and provided two assists in eight competitive games this season.
Joao Mario is a familiar face, having flopped at Inter, but he is surprisingly on the bench along with Petar Musa, as David Neres leads the attack.
The first meeting between these sides was the 1965 European Cup Final, won 1-0 by Inter, while last season the Italians won the quarter-final 5-3 on aggregate.
Inter: Sommer; Pavard, Acerbi, Bastoni; Dumfries, Barella, Calhanoglu, Mkitharyan, Dimarco; Thuram, Lautaro Martinez
Inter bench: Di Gennaro, Audero, De Vrij, Cuadrado, Klaassen, Asllani, Carlos Augusto, Bisseck, Darmian, Sarr, Alexis Sanchez
Benfica: Trubin; Bah, Morato, Otamendi, Bernat; Orkun Kokcu, Joao Neves; Di Maria, Aursnes, Rafa Silva; Neres
Benfica bench: Samuel Soares, Kokubo, Cabral, D Jurasek, Goncalo Guedes, Tengstedt, Joao Mario, Chiquinho, Musa, Tomas Araujo, Antunes Gouveia, Florentino
Ref: Makkelie (NED)