Background-Burullus Lake has brackish water and agricultural, industrial and sewage drainage water represent the major inflows and it represents one of the most subjected lakes to serious pollutants at the delta's coastline. Mugil cephalus is one of the most important food fish species for the Egyptian people. This study was conducted to explain the effect of water pollution of both Qarun and Burullus Lakes on some biochemical and histological characteristics of mullet collected from both Lakes. Our results showed that water collected from Burullus Lake has higher levels of lead and cadmium than Qarun Lake. The liver function analysis showed that there were no significant differences between levels of GGT in M. cephalus livers collected from both Lakes. ALT and AST were significantly increased in livers of fishes collected from Qarun Lake than Burullus Lake, cholesterol, triglycerides, RF1, RF2, high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) in muscles of the mullet collected from Burullus Lake were highly significant increase, while total proteins were significantly decreased in comparison with mullet of Qarun Lake. Histopathological investigations revealed that livers of mullet cached from both Lakes were suffered from marked area of hemorrhage, aggregates of hemosiderin granules and vacuolated hepatocytes. Ultrastructural observation showed degenerated and swelled cylindrical mitochondria in liver obtained from Burullus Lake with accumulation of lipid droplets and degenerated cytoplasmic organoids. Hepatocyte from Qarun Lake showed apoptotic nuclei, degenerated, swelled and cylindrical mitochondria, lipid droplets and dilated rough endoplasmic reticulum. Von Kupffer cells in liver of both lakes contained abundant lysosomes with corrugated walls and numerous cytoplasmic vacuoles. The kidney sections of mullet of both Lakes showed necrosis in the tubular epithelial lining with scattered apoptotic cells and interstitial inflammatory infiltrate.