Background: Sickle cell disease (SCD) is a group of inherited chronic multisystem disorders, being one of the most common hereditary diseases in Brazil.[1] In a modelled US cohort, life expectancy of individuals with SCD was estimated to be 22 years lower compared to the general population (54 versus 76 years, respectively).[2] The life expectancy at birth in Brazil, for the general population, is 77 years.[3] However, little is known about the impact of SCD in mortality in Brazil. The aim of this study was to better understand the patters of mortality of SCD individuals, compared to the general population, using real-world data from Brazilian public databases.Methods: We retrieved data from all registered deaths in Brazil from 2015 to 2019 from the Brazilian public database of the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM). To identify records from individuals with SCD, we selected records with an ICD-10 code referring to SCD (D57, D57.0, D57.1, D57.2 or D57.8) in any field related to cause of death. Using descriptive statistics, we explored the sex, race, age at death, and cause of death recorded in the registries. We also estimated the crude mortality rate of individuals with SCD (per 100.000 inhabitants) and compared the rates from each year with Pearson's correlation. Sensitivity analyses were conducted considering only registries with SCD as the primary (underlying) cause of death. All analyses were conducted with R, version 4.1.0.Results: A total of 6,553,132 deaths were registered in Brazil, from which 3,320 records were from individuals with SCD. Among them, the median age at death was 32.0 (IQR 19.0 - 46.0, Figure 1a), 37 years younger than the general population (median 69.0; IQR 53.0 - 81.0, Figure 1b). Considering only records with SCD as the primary cause of death, we identified 2,603 records. Among them, the median age at death was 30.0 (IQR 19.0 - 45.0). Similar results are observed in subgroup analyses according to sex and race (Table 1). Among registries from individuals with SCD, most were brown or black (79%) and women (52%). In comparison, in the general population, 45% of registries were from brown or black individuals, and 44% were from women. Over the five years evaluated, the crude annual mortality rate of SCD population was 0.32 per 100.000 inhabitants of the general population; considering only deaths with SCD as a primary cause, the mortality rate was 0.25 per 100.000 inhabitants. We did not observe substantial changes or statistical trends in the yearly mortality rate over the period evaluated (from 0.30 to 0.34; Pearson's r = -0.21; p = 0.735). The most common causes of death among individuals with SCD related mortality were sepsis (24.2%) and respiratory failure (7.9%).Conclusions: In Brazil, SCD is associated with a reduction of approximately 37 years on median age at death, in comparison with the general population; data was consistent when stratified by sex and race. This result is similar compared to two other studies: one considering the US context and one evaluating a Brazilian cohort from a reference local center, observed a loss of more than 20 years in the life expectancy of SCD patients at birth.[3, 4] As expected, the main causes of deaths were septicaemias and respiratory failure.[4, 5] Possible misdiagnoses, inaccurate completion of death certificates and possible confounding due to regional differences not accounted in these analyses are the main limitations of our study.