This study aims to monitor physico-chemical parameters and heavy metal (HM) levels in the water, HM levels, and haemato-biochemical changes in parasite-infected and non-infected catfish, Clarias gariepinus, in wild and cultivated origins. The outcomes of physico-chemical properties and heavy metal (HM) levels in water revealed significant variations between the two selected sites, except for cadmium metal (p < 0.05). HM concentrations in both water and organs of the two catfish origins decreased as the following decreased: Fe < Zn < Pb < Cu < As < Cd. Furthermore, the concentration of vital HM was significantly lower in wild catfish as compared to cultivated catfish, whereas non-vital HM was significantly higher in wild catfish. However, the HM accumulation in the different organs of catfish is ranked in ascending order: liver > gills > intestine > muscles. The hematological and biochemical investigations revealed a significant decline in the hemoglobin value, packed cell volume, number of red blood cells, albumin, total protein, and globulin while total aspartate aminotransferase activity, white blood cell count, alanine aminotransferase activity, glucose, and urea levels were all significantly higher in parasitic-infected catfish from two origins compared to uninfected catfish. Human health hazards, as evaluated by non-carcinogenic risk (hazard index and target hazard quotient), estimated daily intake, and carcinogenic risk, were all below the benchmark's allowable range. Nonetheless, the outcome of the health risk assessment suggests that consumption of the muscles of catfish from wild and cultivated origins cannot pose considerable health risks for children and adult consumers. Additionally, the prevalence of parasites can be used as a surrogate indicator to predict the possible impact of metal pollution and bioaccumulation. Consequently, this study suggests that Egypt's environmental management conducts routine HM monitoring in the studied sites to reduce potential health risks.