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Toxic metal pollution influences the lives of diverse aquatic organisms and humans who consume contaminated aquatic products. However, its potential impacts on aquatic organism health and, thus, ecological health, have been neglected in many regions. This research was carried out to contribute to filling that knowledge gap. Three freshwater fish species in the Nhue–Day River basin, Vietnam, have been chosen to study the bioaccumulation of metals (Zn, Cu, Pb, and Cd) in the tissues (livers, kidneys, gills) and their effects on fish physiological health (changes in the oxidative-GST activity, and physiological biomarkers-energy reserves, respectively) from 2013 to 2017. The extensive results revealed significant spatial and temporal variations in metal concentrations in tissues of common carp (Cyprinus carpio), silver carp (Hypothalmic molitrix), and tilapia (Oreochromis niloticus), and well correlated to their concentration in the water (p < 0.05). Fish bioaccumulated metals in the following order: Zn > Cu > Pb > Cd, with more in the kidneys and livers (spring and summer) than in other tissues. Metal accumulation in O. niloticus and C. carpio was higher than in H. molitrix. Biomarker responses (except for glycogen variation) were also higher during warm seasons. Changes in metal levels in water and fish tissues caused variations in biomarkers in the respective fish tissues, particularly in the livers, as demonstrated by significant correlations of metal concentrations in water and fish tissues to biochemical and physiological responses (p < 0.05). The findings suggest that metal pollution in the river basin adversely impacts the physiological health of both wild and cultured fish. Seasonal shifts in the levels of metal accumulation and biomarkers could be connected to species-specific differences in physiology and the levels of metals in environments. This biomarker set is simple but effective in assessing the impact of metal pollution on fish health and, hence, the aquatic ecosystem. This is one of the first biomonitoring studies to assist in designing better water management strategies for the Nhue–Day River basin. Full article

(1) Background: Metal pollution in the Nhue-Day River basin has impacted approximately 12 million people. However, none of the previous studies considered the entire basin’s environmental and health risks. Thus, this research aims to fill knowledge gaps and reduce risks. (2) Methods: Sediment and fish samples from the basin were analyzed to determine the levels of Zn, Cu, Pb, and Cd pollution and their potential ecological (EF, modified Pollution Index—mPI, and expanded, modified potential ecological risk index—emRI) and human health risks (THQ, HI, and TR indices). (3) Results: Metal levels in sediment exceeded Canadian aquatic life protection guidelines, indicating moderate to severe contamination (EFs: 1.3–58.5 and mPIs: 4–39). Compared to the new proposed ecological risk threshold, all river sites and Site 1 for ponds had elevated metal levels; and these posed a very high ecological risk in spring (emRI > 4.5), with Cd being the most hazardous. Lead levels in all fish tissues surpassed Vietnamese and EU food regulations. In agreement with THQ, EWI (Zn, Cu) and EMI (Cd) were both less than 2.5% of the PTWI and PTMI, respectively. However, HI values of 0.67–1.26 suggested a moderate health risk. Carcinogenic risk (TR > 10⁻⁶; estimated for Pb) was detected in several localities for Common carp and Tilapia during the warm season. (4) Conclusions: Metals had a negative impact on the basin’s ecosystem, with Cd being the most dangerous. Because of lead, consumption of Common carp and Tilapia from the basin may pose both non-carcinogenic and carcinogenic health concerns. Full article