Objectives: Erythema nodosum leprosum (ENL - leprosy Type 2 reaction) is a severe immune-inflammatory complication of leprosy that frequently affects patients at any stage of the disease, even after release from multidrug therapy (MDT). Its effect on the patient’s health related quality of life (HRQoL) was evaluated with the SF-36 in a group of 59 multibacillary patients at the Fiocruz leprosy outpatient clinic in Rio de Janeiro. Results: A total of 40 patients with ENL or a history of ENL, 19 patients with neuritis, Type 1 reaction or no reaction, of which six patients had never experienced reactions were recruited. Patients with acute ENL episode had significantly lower scores than patients with recurrent episodes in the mental health (P ¼ 0·036) and the role physical (P ¼ 0·03) domains. Patients with active ENL (new or on treatment) had the lowest scores on all domains of both physical and mental health components. They were significantly more affected in the bodily pain (P , 0·01), physical functioning (P ¼ 0·037) and general health (P ¼ 0·04) domains than patients with no reaction at the time of interview. In general, ENL patients have reduced quality of life, especially in the physical health component. Conclusion: Larger studies of HRQoL of people affected by leprosy are needed to give a more detailed picture of the impact of ENL. It is clear that leprosy, its complications and sequela affect HRQoL which should be routinely evaluated in the assessment of patients to improve care.