ABSTRACT Introduction: The perception of prejudice against, and stigmatization of, sickle cell disease (SCD) leads the patient to perceive a different treatment, due to the disease stigma and maybe related to a worse quality of life (QoL). Objectives: Describe and evaluate the perception of the prejudice against the disease and its impact on the quality of life of patients with sickle cell disease. Methods: This is a cross-sectional study conducted between March 2019 and February 2020, with patients diagnosed with SCD. Patients were questioned about the perception of prejudice in any kind of situation, choosing between “Yes” or “No”, not differentiating situations related to prejudice. To assess the QoL and impact of the disease, the volunteers answered a version of the SF-36 questionnaire translated and validated into Brazilian Portuguese. Results: In this study, 113 patients with SCD were followed up, 92% were classified as HbSS and the rest, divided between HbSC and HbS-β-0. Regarding the SF-36, the worst scores were in the summary of the physical components (mean 48.19 ± 21.51) and the physical aspect had the lowest mean (30.75 ± €42.65). When questioned if they had already perceived any kind of prejudice, including the SCD, 32.74% answered “Yes”. For this comparison, there was a significant difference in the summary of the physical and mental components, with worse QoL for those who had already suffered prejudice. Conclusion: Patients diagnosed with SCD who reported perception of prejudice had statistically significant worse QoL, revealing the negative impact, that might lead to sadness and social isolation.