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Mercury in the aquatic environment can lead to exposure of the human population and is a known toxic metal due to its capacity for accumulation in organs. We aimed to evaluate the mercury level in the blood and urine of fishermen and correlate it with the level of oxidative stress in blood cells. We show in this case-control study that the fishermen of the exposed group (case) of Mundaú Lagoon (Maceió - Alagoas, Brazil) have higher concentrations of total mercury in the blood (0.73–48.38 μg L−1) and urine (0.430–10.2 μg L−1) than the total mercury concentrations in blood (0.29–17.30 μg L−1) and urine (0.210–2.65 μg L−1) of the control group. In the blood cells of fishermen, we observed that the lymphomononuclear cells produced high levels of reactive oxygen species (61.7%), and the erythrocytes presented increased lipid peroxidation (151%) and protein oxidation (41.0%) and a decrease in total thiol (36.5%), GSH and the REDOX state (16.5%). The activity of antioxidant system enzymes (SOD, GPx, and GST) was also reduced in the exposed group by 26.9%, 28.3%, and 19.0%, respectively. Furthermore, hemoglobin oxygen uptake was decreased in the exposed group (40.0%), and the membrane of cells presented increased osmotic fragility (154%) compared to those in the control group. These results suggest that mercury in the blood of fishermen can be responsible for causing impairments in the oxidative status of blood cells and is probably the cause of the reduction in oxygen uptake capacity and damage to the membranes of erythrocytes. • Fishermen's blood that living around Mundaú lagoon (Brazil) has a higher Hg level. • Fishermen's lymphomononuclear cells produced 61.7% more reactive oxygen species. • In erythrocytes of fishermen, mercury induces oxidative damage in biomolecules. • The enzymatic antioxidant system was no efficient in erythrocytes of fishermen. • Fishermen's oxygen uptake and membrane integrity of erythrocytes were compromised. [ABSTRACT FROM AUTHOR]