Background. Pemphigus is an autoimmune blistering disease mediated by autoantibodies directed against keratinocyte adhesion molecules. Leptin, an adipocyte-derived hormone, plays a role in immune responses and promotes autoimmunity. Objectives. This study was conducted to determine whether serum leptin levels are altered in pemphigus patients and whether there is any correlation between leptin levels and the severity of disease. Methods. This study included 47 newly diagnosed patients with pemphigus and 43 age- and sex-matched healthy controls. Clinical characteristics and pemphigus area and activity score (PAAS) were assessed. Serum leptin levels (ng/mL) were measured by a commercial enzyme-linked immunosorbent assay (ELISA). Results. Patients did not differ significantly in serum leptin levels from healthy controls (median (range): 10.8 (0.1–110) ng/mL versus 12 (0.5–69.9) ng/mL and P = 0.53). There was no significant association between serum leptin concentrations and severity of disease measured by PAAS (r s = 0.06, P = 0.70). Conclusion. The results suggest that pemphigus does not have a direct influence on serum leptin levels and the pathogenesis of pemphigus seems to be not dependent on the connection with adipose tissue.