Romelu Lukaku and Lautaro Martinez are supported by Marcelo Brozovic and Hakan Calhanoglu against Spezia, as Inter try to boost confidence with a more convincing performance.
It kicks off at San Siro at 19.45 UK time (18.45 GMT).
The Nerazzurri scraped a stoppage-time victory away to Lecce in their season opener thanks to Denzel Dumfries and he is rewarded with a starting spot this time around, while Alessandro Bastoni also returns to the XI.
Lukaku and Lautaro Martinez are supported by Brozovic and Calhanoglu, with Federico Dimarco preferred to Robin Gosens.
Spezia opened their campaign with a 1-0 win over Empoli thanks to the M’Bala Nzola goal.
Daniele Verde joins Kelvin Amian, Salva Ferrer and Janis Antiste on the treatment table.
Inter: Handanovic; Skriniar, De Vrij, A Bastoni; Dumfries, Barella, Brozovic, Calhanoglu, Dimarco; Lautaro Martinez, Lukaku
Spezia: Dragowski; Caldara, Kiwior, Nikolaou; Gyasi, Bourabia, Sala, S Bastoni, Reca; Agudelo, Nzola