Paramoeba perniciosa is a parasite that has been found in blue crabs Callinectes sapidus from coastal embayments from Florida to Connecticut and has been associated with mortalities in crab shedding facilities in coastal bays of Maryland and Virginia. Hemolymph samples from more than 7300 crabs over a 9-year period from the Gulf (N = 228) and Atlantic (N = 7167) coasts of the United States revealed 0.5% of crabs assayed to be infected by P. perniciosa. Infections were limited to crabs collected from Virginia to New Jersey; Rehoboth Bay, Delaware, had a considerably higher prevalence than other sites sampled. Infections were not present or detected in Gulf coast crabs. Areas reported with P. perniciosa in blue crabs overlap areas reported with paramoeba-like infections in the American lobster Homarus americanus and rock crabs Cancer irroratus. One lesser blue crab Callinectes similis sampled from a Maryland coastal bay was infected by a Paramoeba sp. morphologically similar to P. perniciosa in the blue crab. Actual prevalence of Paramoeba spp. in Callinectes spp. crabs may be higher than reported here due to assay methods. Parasites can cause mortalities in crab populations to the extent that numbers are significantly reduced and therefore disease may need to be considered in fishery models.