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Heavy metals environmental pollution has become a global menace requiring constant biomonitoring and concerted efforts towards its reduction. There are reports of heavy metals pollution of Usuma River, Gwagwalada, Federal Capital Territory, Nigeria. However, information on the direct and indirect health impacts of such pollution on inhabiting fish and on their human consumers are non-existent, especially in Oreochromis mossambicus. The analyses of the physicochemical parameters of Usuma River water, fish heavy metals, histopathological changes, and health risks were performed according to standard procedures. The physicochemical characteristics of the Usuma River water were within acceptable ranges. The Pb bioaccumulation at 2.5100 ± 0.42 mg/kg was significantly (p < 0.05) higher than the values recorded for Cd at 0.4267 ± 0.16 mg/kg and zinc at 0.6027 ± 0.02 mg/kg. Nevertheless, Pb and Cd bioaccumulated more than their recommended permissible levels. Human health risks assessment revealed no immediate carcinogenic risk at a target rate of between 1.2690 × 10 -5 - 2.3530 × 10 -5 . The current heavy metals' concentration posed no long-term non-carcinogenic risk at a hazard index of less than one. This is because the target rate figure above 1.0 × 10 -3 and the hazard index figure above one signifies great health risks. The recorded gills and hepatic cellular changes did not affect organ functionalities as their obtained degree of tissue change figures were all below 10 based on the protocol. Although there was a positive strong correlation between the water temperature and its biochemical oxygen demand as well as between the water dissolved oxygen content and gill cellular changes, a negative strong correlation existed between the water pH and its electrical conductivity and total dissolved solids. The findings highlighted the progressing volatility of heavy metals pollution dynamics within the study area that could pose great human health risks, if unchecked., Competing Interests: Declarations Ethical approval The University of Abuja Ethics Committee on Animal Use (UAECAU) approved the work with Reference no.: UAECAU/2021/004. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)