Organochlorine compounds, such as organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) easily accumulate and persist in the environment. The present study aimed to estimate the residue levels of organochlorine pesticides and polychlorinated biphenyls in water and tilapia fish muscles of the Lake Burullus, Egypt. Nineteen water samples were collected from three locations (Lake Burullus, the nearby Mediterranean Sea and the Lake's drains); while fish samples were collected from three sectors (eastern, middle and western) of the Lake. The levels of organochlorines in water of Lake Burullus were: total hexachlorocyclohexanes (HCH)(0.97-7.75 ng/l), total dichloro-diphenyl trichloro-ethane (DDT) (≤3.88ng/l), total cyclodienes (2.29-22.88 ng/l) and total polychlorinated biphenyl (PCB) (44.05-314.74 ng/l). Whereas, the levels of organochlorines in O. niloticus fish were: total HCH (0.098-0.255 ng/g), total DDT (0.031-0.535 ng/g), total cyclodienes (0.478-0.963 ng/g) and total PCB (19.019-54.812 ng/g). The results revealed that the polychlorinated biphenyls were the major pollutants in Lake's water followed by cyclodienes, HCH and finally DDT. Organochlorines levels of water samples in Lake Burullus were within the permissible limits set by USEPA. Moreover, organochlorines levels of fish samples from Lake Burullus were lower than the maximum permissible levels set by the US Food and Drug Administration (FDA). The concentrations of organochlorines in water and O. niloticus fish in the Lake Burullus should be continuously monitored to avoid the risk effects of organic pollution.