Background: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease. The pathogenesis of CSU is still not completely understood in most cases.The association between CSU and obesity suggests a potential role for adipokines, mainly leptin, which have variable proinflammatory function. Objective: To assess serum leptin levels in CSU patients and their relation to disease activity. Patients and Methods: A case-control study, involving 60 patients with chronic spontaneous urticaria and 30 controls, was conducted at the Allergy Clinic of Ain Shams University hospital. CSU patients were graded as mild, moderate, and severe according to urticaria activity score 7(UAS7). The serum leptin levels were compared among different study groups. Results: Serum leptin levels were significantly higher among CSU patients than control group (p < 0.001), with a positive correlation with urticaria activity (P value <0.001 and r = 0.691). Conclusion: Serum leptin levels are increased in CSU, leptin could have an important role in the pathogenesis of CSU.