Tuesday's game at the Adriatico Stadium will be Nigel Worthington's last as Northern Ireland manager and he will be without two of his most experienced campaigners, while he also has doubts over Jonny Evans and captain Aaron Hughes.
Lee Camp and Grant McCann withdrew on Saturday while Kyle Lafferty is banned.
Goalkeeper Maik Taylor is set to play at the age of 40 for a NI team out of contention for a qualifying spot.
Northern Ireland have endured a disappointing qualifying campaign and last week's 2-1 home defeat to Estonia, their third straight loss, ended any hopes of claiming a play-off berth.
The Azzurri have conceded just two goals in qualifying and have found the back of the net 17 times in nine games.
"They are among the strongest teams in the world," said Worthington. "Prandelli has done a good job to renovate the team."