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Objectives To assess depression and quality of life in individuals with Stargardt’s disease (SD), macular dystrophy whose central vision loss begins in the first decades of life. Methods This observational, cross-sectional study included 41 SD patients and 46 healthy controls, aged 18 to 63 years old, in Minas Gerais, Brazil. Major depression episode was assessed by the Mini International Neuropsychiatric Interview, depressive symptomatology by the Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAM-D) and quality of life by the National Eye Institute Visual Function Questionnaire. The comparison between sociodemographic variables, quality of life and depression was performed using Fisher’s exact test and Mann-Whitney-Wilcoxon test. Results The prevalence of depression was 12.2% in the sample with SD while in the control group was 8.7% (p = 0.614). No significant differences were observed between patients and the control group regarding the prevalence of depression and sociodemographic variables. Patients with SD had overall lower quality of life scores (59.7 vs. 88.7, p < 0.001), and presented inverse correlation between depressive symptoms, as assessed by BDI (Rho = -0.49, p < 0.001) and by HAM-D (Rho = -0.45, p = 0.003) with quality of life scores. Conclusion Depressive symptoms were the major factors affecting quality of life, regardless of sociodemographic data. Individuals with SD may develop copying strategies, seek mental care to prevent the increase of depression and decrease of quality of life.