Environmental exposure to uranium and its daughter radionuclides, has been linked to several negative effects such as those related with important physiological processes, like hematopoiesis, and may also be associated with genotoxicity effects. Herein, genotoxic effects, immunotoxicity, trace elements and C reactive protein (CRP) analyses, were performed in peripheral blood samples collected from individuals of a population living near a deactivated uranium mine. C reactive protein analysis was performed to exclude candidates with active inflammatory processes from further evaluations. DNA damage and immunotoxicity (immunophenotyping and immune cell counts) were detected by comet assay and flow cytometry, respectively. Significant DNA damage was observed in the peripheral blood samples from volunteers living in the Cunha Baixa village. A significant decrease of NK and T lymphocytes counts were observed in the individuals from the Cunha Baixa village, when compared with individuals from the reference site. Uranium and manganese levels were significantly higher in the Cunha Baixa village inhabitants. On the other hand, zinc levels were significantly lower in those individuals when compared with the volunteers from the control village. Results suggest that inhabitants from Cunha Baixa have a higher risk of suffering from serious diseases such as cancer, since high DNA damages were observed in peripheral blood leukocytes and also decreased levels of NK and T cells, which play an essential role in the defense against tumor growth.