The Japan international had missed Brighton's 1-1 home draw against Everton in the Premier League at the weekend with the same issue.
Mitoma was also sidelined with an ankle injury in December but was called-up to the Japan squad for the Asian Cup, which concluded earlier this month. Japan were knocked out by Iran in the quarter-finals.
Mitoma has three goals and six assists in 26 appearances across all competitions for Brighton this season.
"I think we (have) lost Mitoma until the end of the season," De Zerbi told reporters ahead of Wednesday's FA Cup fifth-round clash against Wolverhampton Wanderers.
"It's an important problem. I think two or three months, finished (for) the season."
The Italian said Irishman Evan Ferguson (19) will miss the game at Molineux through injury. Fellow forward Danny Welbeck (33) also has a problem and will be assessed, while defender Joel Veltman (32) will be out.
Brighton, seventh in the Premier League standings after picking up 39 points from 26 matches, visit 12th-placed Fulham in the top flight on Saturday, followed by a trip to AS Roma for their Europa League last 16 first leg on March 7th.
