Lazio hope to get back on track with Taty Castellanos and Mattia Zaccagni, but face a tricky trip to relegation-threatened Cagliari.
It kicks off at the Unipol Domus at 19.45 GMT.
The Biancocelesti lost 2-1 to Fiorentina last week and then were beaten in the Europa League away to SC Braga on Thursday evening, but still managed to win the league phase of the tournament anyway.
The injury crisis is beginning to ease, as Matteo Guendouzi returns from flu symptoms and Zaccagni is available again after suspension.
However, Lazio are still missing Nuno Tavares, Patric, Matias Vecino and Manuel Lazzari, while Loum Tchaouna is potentially heading for a deadline day transfer.
Coach Marco Baroni must watch from the stands, as he sits out a touchline ban.
Cagliari have a precious opportunity to break away from the bottom three, as they are currently only one point clear of the drop zone.
A great run saw them pick up seven points from three rounds until the 2-0 defeat away to Torino.
Zito Luvumbo and Giuseppe Ciocci are still out of action, so Roberto Piccoli is supported by Nicolas Viola, Mattia Felici and Nadir Zortea.
Cagliari vs. Lazio line-ups and live updates
Cagliari: Caprile; Zappa, Mina, Luperto, Augello; Makoumbou, Adopo; Zortea, Viola, Felici; Piccoli
Lazio: Provedel; Hysaj, Gila, Romagnoli, Marusic; Rovella, Guendouzi; Isaksen, Dia, Zaccagni; Castellanos
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