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Vitiligo is an acquired depigmenting disorder due to the destructive loss of melanocytes, clinically presenting as hypopigmented or depigmented macules and/or patches. Many theories have been proposed to explain its etiopathogenesis among which cell-mediated immunity is one of the crucial links. Estimation of vitiligo activity and extent in a patient is important in tailoring an optimal treatment regimen. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (HsCRP) are sensitive indicators for systemic inflammation and are found to be relevant in determining vitiligo disease activity. This study was conducted to estimate serum levels of IL-6 and HsCRP in vitiligo patients and to correlate them with the disease activity and extent in order to assess if these serum markers serve as objective indicators of vitiligo disease activity. This was a hospital-based cross-sectional study of 58 vitiligo patients diagnosed clinically irrespective of age, gender, and any ongoing or past treatment. Disease activity and extent were calculated using the vitiligo disease activity (VIDA) score and vitiligo area severity index (VASI), respectively. Serum levels of IL-6 and HsCRP were obtained and their correlation with VIDA and VASI values were statistically analyzed. A weak negative statistically insignificant correlation was found between IL-6 and VIDA (P = 0.092). No correlation was found between VIDA and HsCRP (P = 0.998). A weak positive, statistically insignificant correlation was found between VASI and IL-6 as well as between VASI and HsCRP (P = 0.175 and P = 0.238, respectively). Although statistically insignificant, the patients who were not on immunosuppressive therapy showed higher mean values of IL-6 and HsCRP compared to those who were on immunosuppressive therapy. In contrast to the findings of previous studies, our study found a weak negative correlation between VIDA and IL-6 levels possibly attributable to the difference between the mean levels of IL-6 among the subgroups of patients who were, and were not on immunosuppressive therapy. The VIDA score and HsCRP levels did not show any statistical correlation. However, patients who were not on immunosuppressive therapy showed a higher albeit statistically insignificant mean value of HsCRP. Our observations suggest that any ongoing and/or treatment in the recent past, especially immunosuppressive therapy, and any co-morbidities should be essentially considered while investigating for sensitive serum markers of inflammation as determinants of vitiligo disease activity., Competing Interests: There are no conflicts of interest., (© 2024 Published by Scientific Scholar on behalf of Journal of Cutaneous and Aesthetic Surgery.)