Federico Bernardeschi, Manuel Locatelli, Matteo Pessina and Alessandro Bastoni are expected to start Italy’s World Cup qualifier against Lithuania.
It kicks off in Vilnius on Wednesday at 19.45 UK time (18.45 GMT).
The Azzurri won their first two games in the group, 2-0 against both Northern Ireland and Bulgaria.
More changes are expected for coach Roberto Mancini, especially as Marco Verratti also pulled out of the squad with a thigh injury.
This means Sassuolo midfielder Locatelli takes the reins, flanked by Lorenzo Pellegrini and Atalanta’s Matteo Pessina.
Mancini said that Atalanta defender Rafael Toloi could get his debut, but perhaps as a substitute, with Francesco Acerbi and Alessandro Bastoni tipped to start.
Giovanni Di Lorenzo of Napoli can get a run-out at right-back, with Emerson Palmieri on the left.
Although the coach did suggest Bernardeschi could have a False 9 role, Ciro Immobile is still the favourite to start in the centre of a trident attack.
He could be flanked by Juventus men Federico Chiesa and Bernardeschi.
Lithuania: Svedkauskas, Mikoliunas, Gaspuitis, Beneta, Vaitkunas, Simkus, Novikovas, Dapkus, Eliosius, Lasickas, Cernych
Italy: G Donnarumma; Di Lorenzo, Acerbi, Bastoni, Emerson; L. Pellegrini, Locatelli, Pessina; Chiesa, Immobile, Bernardeschi