Background: Vitiligo is a multifactorial acquired depigmenting skin disorder with poorly understood etiology. It is characterized by white macules and patches due to loss of functioning epidermal melanocytes. The most widely accepted hypothesis is the autoimmune-mediated melanocyte destruction through the interplay between cellular immunity, humoral immunity, and cytokine action. Peri-lesional vitiligo skin biopsies revealed CD8+ cytotoxic T (cT) cell infiltration proposing a cytotoxic attack against melanocytes. It has been hypothesized that IL-15 might play a role in this autoimmune disease; thus, inhibiting IL-15 activity might be a breaking new therapeutic strategy in the treatment of vitiligo. Objective: The current study was conducted to assess the serum level of IL-15   in patients with non-segmental vitiligo, and to correlate its levels with disease duration, extent, and activity. Patients and methods: The present study was a case-control study conducted on three groups of subjects attending the Dermatology Outpatient Clinic in Mansoura University Hospitals: 30 patients suffering from active non-segmental vitiligo, 30 patients with stable non-segmental vitiligo, and 30 age- and sex-matched healthy controls. Results: Healthy controls and vitiligo cases demonstrated insignificant differences in terms of the demographic characteristics as well as the risk factors. IL-15 level demonstrated insignificant correlation with the gender, smoking, stress, and clinical type in both vitiligo groups. Higher IL-15 level was suggested to be independent risk predictor for vitiligo occurrence and severity but not activity. Conclusion: It could be concluded that, vitiligo cases were associated with a significant elevation in IL-15 level.