The present study was carried out to investigate parasites of one from the most important seafood, the blue crab Portunus pelagicus. Samples of crabs were caught seasonally fromRas El Bar, Damietta, Egypt. Results showed that crabs were infested with two different parasites (protozoa and nematode larvae). The identification of protozoa was confirmed by using the electron microscope. The current study revealed that only 30% of P. pelagicus were infected with parasites. Protozoan parasites showed a prevalence of 79.63%, while nematode larvae showed a prevalence of 20.37%. Histological examination of infected tissues showed disruption of tissue cells, loss of normal gill structure, interruption of lamellae, presence of several granulomas. Also, gonad follicles showed degeneration in the infected crabs. The histopathological effects of such parasites could induce host injury especially in case of heavy infection. However, the highest infection of parasites was recorded in the crabs with a medium size (carapace width 10.1-15 cm & length 6.1-9 cm). whenever the least infection was recorded in the heaviest crabs. Alternatively, the present study may lead to the conclusion that heavy crabs are believed to be healthier for the consumers as it was less susceptible to parasite infection.