The concentrations of four heavy metals (Zn, Fe, Cu, and Pb) in water, sediment, and tissues (gill, muscle, brain, and intestine) of Oreochromis niloticus from a segment of the Lagos Lagoon complex were monitored for 10 months (July 2012-April 2013) spanning wet and dry seasons. Three sampling stations were selected: Ologe Lagoon, the nearest to the point where effluent is discharged from Agbara Industrial Estate, the Owo River is upstream before the point of discharge of industrial effluent, and Etegbin is downstream. In most cases, the highest concentrations of heavy metal in fish tissues were recorded in samples obtained from Ologe Lagoon. The ranges of concentrations of heavy metals in the tissues of the fish were 4.06 ± 2.45-49.94 ± 13.11, 81.27 ± 28.52-2044.64 ± 554.77, 10.90 ± 7.69-41.10 ± 11.24, and 0.12 ± 0.07-1.81 ± 3.12 mg/kg for Zn, Fe, Cu, and Pb, respectively. There were significant negative correlations (lowest; r = -0.24, p < 0.01, n = 30; highest; r = -0.58, p < 0.01, n = 30) between fish tissue metal concentrations and size of fish from Ologe Lagoon. Also, significant positive correlations (lowest; r = 0.48, p < 0.05, n = 30; highest; r = 0.93, p < 0.01, n = 30) between concentrations of Cu in sediment and tissues of O. niloticus were observed. The concentrations of the metals in the tissues of O. niloticus have exceeded the limits recommended by WHO. The maximum safe daily consumption (MSDC) value of Fe in Ologe Lagoon was lower than the recommended average daily intake of fish for humans. This indicated that O. niloticus from Ologe Lagoon may not be safe for human consumption. Therefore, there is a need for regular monitoring of heavy metal in these water bodies and enforcement of existing laws on the treatment of effluent before they are discharged into aquatic ecosystems.