Background: Burullus Lake has received a great attention because of its environmental and economic importance for being a significant source of fish production in Egypt. It is subjected to many of environmental changes due to the huge amount of discharges originated from different sources as well as many human activities. The Nile tilapia (Oreochromis niloticus) is an abundant sedentary fish present in the most Egyptian lakes, Nile River, and ponds. The study was designed to evaluate some metal pollution in Burullus Lake. Results: The values of heavy metals (Mn, Zn, Fe, Ni, Cu, and Pb) were measured in lake water and muscles of O. niloticus fish during winter and summer 2014. Water samples were collected from six sampling sites, while fish samples were collected from the three sectors (eastern, middle, and western) of the lake. The mean values of heavy metals (Mn, Zn, Fe, Ni, Cu, and Pb) in surface water of Burullus Lake during winter and summer for the year 2014 were 1.09, 10.50, 29.38, 6.87, 2.05, and 5.98 μg/L, respectively, whereas the annual means of heavy metals (Mn, Zn, Fe, Ni, Cu, and Pb) in the muscles of O. niloticus fish were 0.68, 4.70, 10.62, 0.52, 0.39, and 0.46 μg/g wet wt., respectively. Conclusions: In lake water, Mn was the lowest concentration of the six sampling sites, while Fe was the highest concentration, whereas in fish muscles, Cu recorded the lowest concentration of the three sectors, while Fe was the highest concentration. The southern part of Burullus Lake had the highest heavy metal values as it influenced by the discharge of massive amounts of domestic sewage as well as agricultural and industrial effluents. The accumulation of heavy metals in fish muscles of the three sectors showed different patterns. Generally, the values of metals in the fish muscles were accepted by the international legislation limits and are safe for human consumption.