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Objective: To estimate trends in mortality rate and average age of death, and identify sociodemographic factors associated with early death in patients with sickle cell disease (SCD). Methods: An ecological and cross-sectional study was conducted using data from the Mortality Information System. All deaths of patients residing in the state of São Paulo from 1996 to 2015 with at least one International Disease Code for SCD in any field of the death certificate were included. Simple linear regression was used to estimate trends. The Log-rank test and multiple Cox regression were used to identify factors associated with early death. Results: The age-standardized mortality rate per million inhabitants increased by 0.080 per year (R²=0.761; p<0.001). When the events were stratified by age at death, the increase was 0.108 per year for those occurring at age 20 years or older, (R²=0.789; p<0.001) and 0.023 per year for those occurring before age 20 years old (R²=0.188; p=0.056). The average age at death increased by 0.617 years (7.4 months) per year (R²=0.835; p<0.001). Sociodemographic factors associated with early death identified were male gender (hazard ratio — HR=1.30), white race (HR=1.16), death occurring in the hospital (HR=1.29), and living in the Greater São Paulo (HR=1.13). Conclusions: The mortality rate and the average age of death in patients with SCD have increased over the last two decades. Sociodemographic factors such as gender, race, place of occurrence, and residence were found to be associated with early death. [ABSTRACT FROM AUTHOR]