Melasma, an acquired disorder of hyperpigmentation, is the most common pigmentary disorder in India. Many factors are implicated in the pathogenesis, and recently the role of oxidative damage including melatonin has been postulated. This study was undertaken to evaluate the role of oxidative stress and serum melatonin in pathogenesis of melasma.Seventy-five patients with melasma and an equal number of age and sex-matched controls were included in the study. Clinical characteristics were noted, and baseline severity assessment using modified Melasma Area and Severity Index (MASI) was done in all patients. Serum melatonin, catalase, protein carbonyl, and nitric oxide levels were measured and compared between cases and controls.The serum levels of melatonin and catalase were significantly lower among the cases as compared to controls, while the serum levels of protein carbonyl and nitric oxide were significantly higher in cases compared to controls. There was no statistically significant correlation between these markers of oxidative stress and severity of the disease.Oxidative stress is increased in patients with melasma compared to the control group in this study. A state of melatonin deficit also exists in patients with melasma. No correlation between the oxidative stress and severity of the disease was found. Further and larger studies including therapeutic trials with powerful antioxidants are warranted.