A total of 36 water samples and 600 specimens of the cichlid fish, Oreochromis niloticus Linnaeus 1757; were seasonally collected from three water habitats in the Nile Delta region throughout winter 2016 till autumn 2017. An investigation was conducted to determine the relationship between water analysis and the hematological and parasitological data of studied fish. Thus, the effect of water quality was estimated by using parasites as bioindicators and hematological analysis as biomonitors in the aquatic ecosystem. According to physical and chemical water analysis, a very high significant difference of EC, DO2, BOD5, K+, Na+, Ca+2, Cl-, HCO3-, TDS and SO4+2 was reported between different study sites (p ≤ 0.001). Moreover, hematological studies of fish samples revealed a very high significant difference of G.S.H. and Testosterone in males and G.S.H., MDA and Progesterone in females (p ≤ 0.001), and a highly significant difference of MDA in males (p ≤ 0.01). In addition, a significant difference of CAT of males (p ≤ 0.01) was also detected between different study sites. Parasitologically, there was a significant difference in prevalence, mean intensity, and abundance of C. halli in O. niloticus in different study sites (p ≤ 0.05). Each factor was morphometrically analyzed, and variations were hence discussed. The difference in environmental characteristics, despite the stability of the geographical location, led to variations in both fish blood analysis and parasitic infestation level in the study sites. Therefore, fish and parasites are evidently used as biological biomarkers to assess their environment.