Abstract: Background and Objective: Cymothoid isopods are extremely serious fish parasitic infestations that adversely impact the health of aquatic animals with considerable economic losses. The present study aimed to investigate the massive infestation by the cymothoid isopod, Nerocila bivittata (N. bivittata ) affecting Tilapia zillii (T. zillii ) fish within Lake Qarun Egypt as an attempt to understand the effects of the parasites on the haematological parameters and histopathological alterations in the infested fish. Materials and Methods: A total of 150 T. zillii were collected alive during June, 2016. Fish were thoroughly investigated visually and microscopically for presence of external parasites. Analysis of blood and serum samples from parasitized and un-parasitized fish was carried out. Results: Ninety-six fish (64%) were found to be infected with isopods. All retrieved isopods were further identified as N. bivittata. The isopod was found settled in different parts of fish body but gills were the most predilection site. Parasitized fish had lowered erythrocyte counts, haemoglobin and haematocrit values. Leucocyte counts, total protein, albumen and globulin also decreased in infested fish. Severe histopathological alterations were recorded in the skin, muscles and gills of infested fish. Analysis of water samples collected from the Lake revealed unfavorable values for water quality measures and levels of some heavy metals were higher than the recommended values. Conclusion: The results of this study indicate that N. bivittata are serious parasites in aquaculture and can infect wild fish populations. These parasites feed on the blood of infest fish and put their lives at risk.