Experiments were carried out on adult male zebrafish (Danio rerio) to assess early changes induced by waterborne exposure to different isotopic compositions of uranium (depleted uranium associated or not with U-233). Oxidative stress and neurotoxicity were selected as effect endpoints to characterize uranium chemo- and radiotoxicity. Catalase, glutathione peroxidase, and superoxide dismutase activities and total glutathione content of hepatic extracts, as well as brain acetylcholinesterase activity and uranium bioaccumulation, were measured. Oxidative stress induced by uranium exposure led to decreases in superoxide dismutase and catalase activity levels as well as total glutathione content in liver extracts. These perturbations were significantly more marked in U-233-exposed fish. Furthermore, significant increase in acetylcholinesterase activity was observed in brain extracts at the same level, whatever the isotopic composition of uranium.