Migraine patients have an increased risk to develop deep white matter hyperintensities (WMH) than the general population. Oxidative stress is believed to play a role in the pathogenesis of migraine. The present study was undertaken to assess oxidant/antioxidant balance of migraineurs with and without WMH. We hypothesized that increased oxidative stress and decreased antioxidant response may play a role in the pathophysiology of WMH in migraineurs. The study included 32 patients in the migraine group and 17 age- and sex-matched healthy subjects without headache in the control group. The migraine group comprised 18 with WMH and 14 without WMH. We evaluated oxidative status with malondialdehyde (MDA) and to determine the activities of antioxidant enzymes: superoxide dismutase, glutathione peroxidase and catalase (CAT) in serum of migraineurs and controls. Comparison of the patient and control groups for oxidative parameters revealed significantly lower level of CAT and higher level of MDA in the patient group. Two-way comparison for CAT and MDA of the migraine with and without WMH and the controls revealed that CAT serum level significantly decreased in migraine patients with WMH than migraine patients without WMH and controls. In this preliminary study, we demonstrated that the levels of CAT were decreased in migraine patients with WMH compared to patients without WMH and controls. These findings suggest that decreased antioxidant response may play a role in the pathophysiology of WMH in migraineurs. Besides, our results encourage the new treatment and follow-up options based on antioxidant systems.