Wing Mirco Bergamasco and lock Marco Bortolami have been ruled out of Italy's vital pool game against Wales.
Bergamasco is out with a broken cheekbone
Bergamasco broke a cheekbone in the 19-14 win over Canada on Tuesday, while Bortolami suffered a dislocated clavicle in the same game.
The news is a major blow to Italy's chances of qualifying for the quarter-finals.
They must beat Wales on Saturday to book their place in the knock-out stages of the tournament.
There are also doubts over wing Andrea Masi, who is battling to shake off a hip complaint.
And captain Alessandro Troncon has been plagued by back and shoulder problems but should be fit for the Wales game.
"We're not looking past Saturday," said Italy coach John Kirwan.
"We have a little bit of difficulty in naming our team. Hopefully, we'll get our team out in time otherwise we'll be subject to another fine (under International Rugby Board rules)."
Kirwan echoed his earlier complaints about his side's dire playing schedule.
When the Azzurri face Wales on Saturday they will have played all four of their pool games in the space of 14 days.
"If we play well enough and don't win because we're fatigued, that would be a great injustice," hsaid Kirwan.
"I'm not criticising the organisation because we can't afford the fine."