Tilapia zilli and Solea vulgaris live fish were collected from Lake Qarun, El Fayoum governorate, during mass mortality at summer season. The main clinical sings of infected fish were slimy dark skin with signs of asphyxia, presence of hemorrhagic lesions on the skin, fins, and gills. Investigation of T. zilli fish revealed that either bilateral and/or unilateral infection of their gill chambers with one species of Cymothoidae identified as Nerocila orbignyi. Bacterial isolation identified that 100% of examined fishes were found to be infected with either one type or mixed bacteria. V. alginolyticus was the most common bacteria isolated, followed by A. sobria, then Staph aureus. The results of water analysis showed increase in concentration trace elements especially iron 2.7 mg/l. Therefore, the present investigation was conducted to shed light on multifactorial causes of mass mortalities among fishes in the Lake.