Background: Leprosy is a chronic and complex infectious disease. It affects skin and the peripheral nerves causing nerve damage, pain, visible deformities and disabilities. Leprosy patients suffer from physical, psychological, social discrimination and stigmatization. Objectives: To determine the health-related quality of life (HRQoL) in a group of leprosy patients in Egypt outlining their sociodemographic, dermatological and neurological characteristics. Patients and methods: The study included 300 leprosy patients recruited from Benha Dermatology & Leprosy clinic and Abu Zaabal Leprosarium in Egypt. Patients were subjected to detailed history taking, dermatological and neurological examination (including DN4 questionnaire to assess pain), and assessment of HRQoL using Arabic version of DLQI and WHOQOL-BREF questionnaires. Results: Patient’s mean age was 59.4. 161 (53.67%) were males and 139 (46.33) were females. Lepromatous skin lesions were found in 150 (50.33%), while 137 (45.67%) had cutaneous drug side effects. Pure neurological leprosy was for 12 (4%) patients. Neuropathic pain was diagnosed in 195 (65%) of patients based on DN4 score (≥ 4). World Health Organization (WHO) grade 2 deformities were diagnosed in 62 patients (20.66%). The mean DLQI score was 11.58. Patients had the lowest mean scores in all domains of the WHOQOL-BREF which indicates a marked impairment of HRQoL. Conclusions: Quality of life was impaired in 100% of leprosy patients. In Egypt leprosy causes significant impairment of patients’ HRQoL even in fully treated patients. It is recommended to implement DN4 and WHOQOLBREF questionnaires in research and routine assessment of leprosy patients.