Parasitic infections of Tilapia sp. from the agricultural drainage in the eastern region of Saudi Arabia were examined. The identification of the parasites, the histopathological, and the histo-chemical analysis of the infected fish organs were investigated in series of studies. The present work estimated the intensity and the density of the encysted metacercariae of the Pyigidiopsis summa and geneta in random samples of different fish organs. The study also investigated the effect of these parasites on the serum glucose, total protein, and the activity of the LDH enzyme. The results indicated that all fish in the examined samples (100%) were infected with the encysted metacercariae of the Heterophyd sp. The highest intensity of the metacercariae was found in the liver (43.30%), and its mean density was 17.31±35.68 cyst/cm2. The intensity of the metacercaria in the intestine was 33.37%, and its mean density was 13.34±15.77 cyst/cm2. The lowest intensity and density of the parasite was in the skin, 23.33%, and 9.33±8.87 cyst /cm2 respectively* The biochemical analysis showed a significant increase in the serum glucose, and the activity of the LDH enzyme of the infected fish. However, total protein did not vary much between the infected fish and the uninfected control.