Twenty-one 6-month-old male New Zealand rabbits, weighing 3.5±0.3 kg, were divided equally into a control group and two trial groups. For 70 days, the control group (Group I) received drinking water containing 0.07 mg F–/L, and the second and third groups (Groups II and III) were given water containing 10 and 40 mg F–/L, respectively. On days 0, 21, and 70, blood samples were taken from each rabbit in each group into heparinised tubes. Erythrocyte antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were determined in each blood sample, along with the level of malondialdehyde (MDA). In Group III, by day 70, a significant decrease was observed in SOD activity (74.14% of the control group) and a significant increase in CAT activity (23.92% greater than in the control group). On days 21 and 70, significant increases compared to the control group were found, respectively, in GPx activity (14.85% and 39.29%) and the level of MDA (23.56% and 89.12%). These results indicate that fluoride causes oxidative damage in vivo. When considered in conjunction with other parameters such as urinary fluoride, these changes in erythrocyte antioxidant enzymes may prove useful for diagnosing fluoride poisoning and determining its severity, especially in cases of elevated fluoride exposure levels as studied here.