The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p< 0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p < 0.05). A significant decrease in the control group (p < 0.05) and increase in group 4 (p < 0.05) were observed in GSH level after RAIT (p < 0.05). Mean variation of GSH was significant between control group with groups 3 (p < 0.01) and 4 (p < 0.01). The results indicate that activity of SOD remained unchanged in all groups (p > 0.05). A significant increase was observed in CAT activity after RAIT in all groups (p < 0.05), which was higher in control group than intervention groups. In groups 3 (p < 0.05) and 4 (p < 0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.