Myxosporidiosisis a protozoan parasitic fish disease that causes damages to fish organs and might eventually end with mortalities and deterioration of meat quality of the affected fish. The presence of parasitic infestation is usually accompanied with the production of reactive oxygen and nitrogen species that produces extra damage to host organs and inactivation of antioxidant defense system that increase the intensity of parasitic infestation. Recently, the response of the infested tissue to oxidative stress is varieddepending on the type of parasite; therefore the use of oxidative stress markers as indicator for myxobolus infestation is relevant. In the present study, Oreochromis niloticus was investigated for oxidative stress markers (GST, SOD, NO., H2O2 and MDA) in liver, muscle, spleen and gills infested with myxobolus spp. Histopathological examination was performed to clarify the cellular damageassociated withmyxobolus infestation. Results indicated that there was a non-significant change in GST activity in all organs, while SOD activity was significantly decreased in liver and gills after myxobolus infestation. The concentration of nitric oxide, hydrogen peroxide, and lipid peroxidation were significantly increased in (gills and spleen);(liver, spleen and muscle); (liver and muscles), respectively. Intestine and eyes of the affected fish showed a degenerative changes and replacement of the epithelial tissues with myxobolus spores with CHARacteristiceosinophilic granules that has a role in the immunity of host against parasitic infestation.The phylogentic analysis showed that the identified species of myxobolusin the present study was revealed a close relationship as well as a high identity percentage with, Myxoboluskisutchi and similar tissue tropism which highlighted the use of both molecular identification and oxidative stress markers for diagnosis of myxobolus infestation in dead fish when the parasitological examination alone becomes inadequate foraccurate detection of myxobolus infestation.