"It's a bad, bad situation. It's the back injury which kept him out against Everton (at the weekend). It's an important problem. I think two or three months, (so) finished (for) the season," De Zerbi said ahead of Wednesday's FA Cup tie against Wolves.
The Japan international has scored three goals and provided six assists in 26 appearances in all competitions this season and has been a key player since his return to the south coast in 2022.
Mitoma, 26, has already missed a significant portion of the 2023/24 campaign due to an ankle injury and his participation in the Asia Cup.
This latest injury comes at a crucial time in the season for seventh-placed Brighton as they seek a top-six league finish and are still in contention in the FA Cup and Europa League.
The Seagulls travel to Wolves on Wednesday in the fifth round of the FA Cup and will also be without Evan Ferguson and the suspended Billy Gilmour, whilst Danny Welbeck and Joel Veltman face late fitness tests.
