Inter bring in Arturo Vidal and Denzel Dumfries with Lautaro Martinez and Edin Dzeko, as they seek their first Champions League win against the immensely surprising giant-killers Sheriff Tiraspol.
It kicks off at San Siro at 20.00 UK time (19.00 GMT).
The Nerazzurri suffered a late defeat to Real Madrid and held Shakhtar Donetsk 0-0 in Ukraine, but are yet to score in this season’s Champions League.
Incredibly, Moldovan club Sheriff in their first ever participation in the tournament are top of Group D with a 100 per cent record, having beaten Shakhtar Donetsk 2-0 and won 2-1 away to Real Madrid.
Simone Inzaghi’s men are also fresh from their first Serie A defeat of the season, 3-1 at Lazio, and make changes from the Stadio Olimpico.
Lautaro Martinez returns after international duty to partner Dzeko, but Federico Dimarco steps in for Alessandro Bastoni, Dumfries is preferred to Matteo Darmian and Arturo Vidal comes in for injured Hakan Calhanoglu.
Sheriff started the same XI in their first two Champions League games, but are forced into changes.
Goalkeeper Giorgos Athanasiadis has to pull out, while striker Jasurbek Yakhsiboev makes way for Bruno Souza.
Alexander Belousov is still unavailable in midfield.
Inter: Handanovic; Skriniar, De Vrij, Dimarco; Dumfries, Barella, Brozovic, Vidal, Perisic; Lautaro Martinez, Dzeko
Inter bench: Cordaz, Radu, Gagliardini, Alexis Sanchez, Vecino, Kolarov, Sensi, Ranocchia, Correa, D’Ambrosio, Darmian, Bastoni
Sheriff: Celeadnic; Fernando Costanza, Arboleda, Dulanto, Cristiano; Addo, S Thill; A Traoré, Kolovos, Castañeda; Bruno Souza
Sheriff bench: Pascenco, Radeljic, Julien, Kyabou, Cojocari, Nikolov, Cojocaru, Yansane
Ref: Makkelie (NED)