BACKGROUND: Sickle cell disease is a genetic, hereditary and chronic disease that affects the health of its carriers and might impair their health-related quality of life. OBJECTIVE: The aim of the current study was to assess the health-related quality of life of individuals with sickle cell disease followed at referral centers in Alagoas, Brazil. METHODS: A total of 40 individuals with sickle cell disease aged 12 to 43 years old were evaluated by means of sociodemographic and clinical questionnaires, the Medical Outcomes Study 36-Item Short Form Health Survey and the Beck Depression Inventory. The latter was applied only to adults. RESULTS: Most participants were adults (62.5%) with a predominance of the SS genotype (85%) with pain being the commonest complication (95%). Mood disorder was found in 40% of the adults. The patients exhibited overall impairment of quality of life, which was more pronounced among the adults and under 15-year-old adolescents. Married adults exhibited less impairment of most quality of life domains compared to unmarried adults, and the adults with mood disorder exhibited greater impairment of all quality of life domains. CONCLUSIONS: These results suggest that interventions that aim to improve vitality, pain, and mental health might contribute to maintaining high levels of quality of life in patients with sickle cell disease, especially among adults and under 15-year-old adolescents.