The present study was planned to investigate the effect of Saprolegnia parasitica infection in the hematological, serum biochemical and pathological alterations of gray mullet. Forty five fish were divided into three equal groups. Fish of first group served as a control. Fish of group (2&3) were infected by Saprolegnia parasitica. Fish of group (3) were treated after 7 days of post-infection using sodium chloride 2ppm and 1% Nigella sativa for 10 days. Sampling was done after 1 and 7 days of post-infection (gps 1 & 2) and 10 days of post-treatment (gps 1& 3). The results revealed a non significant changes in the hematological and the biochemical parameters after 1 day of infection, but after 7 days of post-infection and 10 days of post-treatment, a significant decrease in RBCs, Hb, PCV and significant increase in AST, ALT, urea, creatinine, sodium, potassium, cortisol, insulin and glucose were seen. Iron showed a significant decrease at the same period of sampling. The pathological examination revealed a massive fungal growth resembling a tuft of cotton wool threads was seen in eyes, grills, fins and in localized areas of the skin. Microscopically, the fungal hyphae and spores appeared on eyes, gills, skin and underlying muscles with marked degenerative, necrotic and inflammatory reactions. These reactions were evident, after 7 days of postinfection and the severity of the lesions were markedly decreased after 10 days of post-treatment. It could be concluded that, saprolegnia parasitica infections induced marked tissue alterations as well as some hematological and serum biochemical changes. Although sodium chloride treated the infected cases and allowed the regenerative processes but it does not progress the hematological and serum biochemical parameters.