Inter revamp their squad including Davide Frattesi, Benjamin Pavard and Marcus Thuram, as Empoli make their debut under new coach Aurelio Andreazzoli.
It kicks off at the Stadio Castellani at 11.30 UK time (10.30 GMT).
The Nerazzurri have the opportunity to go three points clear at the top of the table, as Juventus lost their unbeaten record with a 4-2 defeat to Sassuolo on Saturday.
Simone Inzaghi rotates the squad after a midweek 1-1 Champions League draw with Real Sociedad, still missing injured Juan Cuadrado and Stefano Sensi.
Frattesi finally gets his first start for the club, while Hakan Calhanoglu has recovered after a muscular issue.
Empoli sacked coach Paolo Zanetti after failing to manage a point or even a single goal in the opening four rounds, culminating in a 7-0 defeat to Roma.
He was replaced by Andreazzoli, who is returning to this club yet again after spells in 2017-18, 2019 and 2021-22.
Goalkeeper Elia Caprile, striker Francesco Caputo and midfielder Daniel Maldini are still out of action, but he brings back Razvan Marin, Tommaso Baldanzi and has a surprise start for 20-year-old Albanian striker Stiven Shpendi.
Empoli: Berisha; Ebuehi, Ismajli, Luperto, Pezzella; Marin, Ranocchia, Maleh; Baldanzi; Cambiaghi, Shpendi
Inter: Sommer; Pavard, Acerbi, Bastoni; Darmian, Frattesi, Calhanoglu, Mkhitaryan, Dimarco; Lautaro Martinez, Thuram
Player statistic
| 26' |  |
Francesco Acerbi | ||
| Giuseppe Pezzella | |
33' |
| 51' |  |
Federico Dimarco | ||
| Youssef Maleh | |
63' | ||
| 65' | |
Alessandro Bastoni |
Match statistic
