Background: The present study investigated the potential roles of plasma lymphocyte DNA damage, the urotensin-2 receptor (UTS2R), and oxidative changes in patients with varying degrees of migraine-related disability who were in the ictal phase and presented to our emergency department. Methods: This study enrolled 40 consecutive adult patients with migraine attack and 40 age-and sex-matched healthy controls. The same health care professional determined the headache-related disability of each patient's migraine attack using the Migraine Disability Assessment Scale (MIDAS); patients were divided into three groups based on MIDAS score. Plasma lymphocyte DNA damage; UTS2R, malondialdehyde (MDA), and catalase (CAT) levels; total oxidant status (TOS); total antioxidant status (TAS); and the oxidative stress index (OSI) were used as predictors of early oxidative changes. Results: Plasma lymphocyte DNA damage, TOS, MDA levels, and OSI values were significantly higher in patients with migraine compared to controls. Conversely, TAS and CAT and UTS2R levels were markedly lower in patients with migraine compared to controls. Comparisons of the patient groups by MIDAS score revealed significant differences in plasma lymphocyte DNA damage and CAT levels but no differences in TOS, MDA levels, OSI, TAS, or UTS2R levels. MIDAS scores were positively correlated with the degree of lymphocyte DNA damage, but neither of these factors was significantly related to CAT levels. Conclusion: The present data suggest that lymphocyte DNA damage and changes in oxidative/ antioxidative status may reflect an enhanced oxidative damage and an ineffective antioxidant defense system in migraineurs during headache attacks. In addition, lymphocyte DNA damage levels may be an indicator of the degree of migraine-related disability as assessed by MIDAS score.