Sandro Tonali, Leonardo Spinazzola and Ivan Provedel are out of the Italy squad to face Ukraine tonight, with reports Giacomo Raspadori will be used as a centre-forward alongside Nicolò Zaniolo.
It kicks off at San Siro at 19.45 UK time (18.45 GMT).
The Azzurri need a victory to catch Ukraine in the EURO 2024 group in second place, with a game in hand, and Luciano Spalletti is expected to make radical changes from the side that drew 1-1 in North Macedonia on Saturday.
Some are forced, because Tonali, Matteo Politano, Gianluca Mancini, Federico Chiesa and Lorenzo Pellegrini are out of action, while it is confirmed that Spinazzola and goalkeeper Provedel will not even be on the bench.
There are differing reports over what Spalletti is planning tonight, including the use of Raspadori as a centre-forward rather than wide in the trident attack, replacing Ciro Immobile.
That would also automatically make Gianluigi Donnarumma the captain as the player with the most senior caps.
Zaniolo is pushing for a starting spot with Lazio’s Mattia Zaccagni shaking off a slight knock.
Manuel Locatelli is battling Bryan Cristante for a midfield place, with Davide Frattesi expected to come in.
Giorgio Scalvini is the favourite to replace injured Mancini in defence.
Italy (probable): 1 Donnarumma; 2 Di Lorenzo, 15 Scalvini, 23 Bastoni, 3 Dimarco; 18 Barella, 5 Locatelli, 8 Frattesi; 21 Zaniolo, 10 Raspadori, 20 Zaccagni
Italy bench: 12 Vicario, 22 Meret, 4 Biraghi, 6 Romagnoli, 13 Darmian, 19 Casale, 14 Pessina, 16 Cristante, 7 Orsolini, 9 Retegui, 11 Gnonto, 17 Immobile