Inter start Romelu Lukaku and Lautaro Martinez again, but bring back Kwadwo Asamoah, while Brescia have Mario Balotelli and Alfredo Donnarumma with a new goalkeeper.
It kicks off at the Stadio Rigamonti at 20.00 GMT.
You can follow all the build-up and action as it happens from this game and Parma-Verona on the LIVEBLOG.
Antonio Conte’s Nerazzurri missed the opportunity to close on leaders Juventus, as both teams were held to draws at the weekend by Parma and Lecce respectively.
The coach complained that he had very few options available to him following an injury crisis, as Stefano Sensi, Alexis Sanchez, Matias Vecino and Danilo D’Ambrosio are still out of action.
It means there is no rest for Lukaku and Lautaro, while Roberto Gagliardini again takes the midfield slot.
Asamoah returns after a knee issue to take the left flank from Cristiano Biraghi, while Diego Godin completes the defence.
Brescia boss Eugenio Corini is already under pressure, with reports Cesare Prandelli is being lined up to replace him just months after taking the team to the Serie B title.
He has more problems to deal with, because goalkeeper Jesse Joronen suffered a knock against Genoa and is not even in the squad, so 31-year-old former Inter shot-stopper Enrico Alfonso has to make his career Serie A debut.
Leonardo Morosini has also been left out, apparently in a technical decision, with Jhon Chancellor, Ernesto Torregrossa, Luca Tremolada, Giangiacomo Magnani, Federico Viviani and Daniele Dessena injured.
Alfredo Donnarumma returns to the starting XI with star man Balotelli, who so far has only one goal to his name in the Rondinelle jersey.
The trequartista role seems to be scrapped, moving to a 3-5-2 formation this evening that mirrors Inter, with 21-year-old Massimiliano Mangraviti brought in.
Inter could win their first five away games of the Serie A season, something this club only achieved in 1966-67, 1997-98 and 2012-13.
Brescia: Alfonso; Mangraviti, Cistana, Gastaldello; Sabelli, Bisoli, Tonali, Romulo, Mateju; A Donnarumma, Balotelli
Brescia bench: Andrenacci, Ndoj, Spalek, Zmrhal, Aye, Matri, Martella, Semprini
Inter: Handanovic; Godin, De Vrij, Skriniar; Candreva, Gagliardini, Brozovic, Barella, Asamoah; R Lukaku, Lautaro Martinez
Inter bench: Padelli, Berni, Ranocchia, Politano, Lazaro, Borja Valero, Dimarco, Esposito, Biraghi, Bastoni