This study aimed to assess the physicochemical quality of the water and the heavy metal of the sediment, water, and flesh of two species of fish most commonly consumed by residents in the lower reaches of the Mono River. To this end, four stations (Ahossanou, Codjohoué, Athiémé, Grand-Popo) were selected and surveyed during high water (October to December 2021) and low water (January to March 2022) seasons to measure physicochemical parameters and examine the ichthyofauna in artisanal catches. Water samples were taken to measure the biological oxygen demand (BOD 5 ), nitrite and nitrate levels. Additionally, samples of sediment, water, and fish flesh were taken to analyze heavy metal concentrations (lead and cadmium). The BOD 5 concentrations exceeded 30 mg•L -1 , indicating poor water quality. All nitrite and nitrate levels were within acceptable limits (3.28 and 44.28 mg•L -1 , respectively). The potential ecological risk posed by sediment contamination ranged from low during high water to considerable during low water seasons. Measured lead and cadmium concentrations in the water exceeded permissible limits (0.05 and 0.005 mg•L -1 , respectively). Brycinus macrolepidotus and Chrysichthys nigrodigitatus were the most abundant fish species caught in the Mono River. While cadmium levels in the fish flesh were below the WHO/FAO standard (0.05 mg•kg -1 ), lead concentrations exceeded the WHO/FAO standard (0.3 mg•kg -1 ). The study concluded that consumption of fish from the lower Mono River poses health risks to local communities.