Phenol is one of the most toxic chemicals on the health status of fish, which produces several endocrine-disrupting effects on fish. This study comprised two parts: one was the field investigation of phenol pollution on male (Oreochromis niloticus) collected from River Nile branch at the vicinity of Coke Factory at Tebin locality (Helwan) and the other was the experimental investigation of phenol on male Oreochromis niloticus collected from a private farm to monitor the effect of phenol pollution on fish reproduction and health status. The levels of natural phenol residues were 1.4 ppm in the liver of fish and 0.02 ppm in the water site of collection. A total of 80 male Oreochromis niloticus were exposed to 30 mg/l phenol for periods of 21, 28, 35, and 45 days while another 20 fish were kept as control. Results found a significant decrease in growth measurements; gonado-somatic index; relative fecundity; sperm density; sperm live %; aspartate aminotransferase (AST). In contrast, total protein; albumin; alanine aminotransferase (ALT); glucose, and estradiol (E2)-were showed a significant increase. Histopathological examination of hepatocytes showed a remarkable degree of necrosis. A significant number of testicular tubules showed complete loss of spermatogenic contents. Electrophoretic analysis of serum for vitellogenin revealed the appearance of two bands in protein marker. The first band appeared after 21, 28, and 35 days, while the second band appeared after 45 days. Ultimately, laboratory investigations concluded that phenol possesses an estrogenic endocrine disrupting effect.