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Background and Purpose: Post stroke fatigue (PSF) is a common and debilitating condition that can last months or even years. Although the relationship between PSF and Health Related Quality of Life (HRQoL) has been studied, the results have been largely inconclusive and not previously reported in a minority cohort.Hypothesis: Higher levels of PSF and Post Stroke Depression (PSD), will predict lower levels of HRQoL in African/Caribbean Blacks.Methods: Prospective, cross-sectional, observational study approved by the IRB. Patients ≥ 18 years old with a stroke in the past 3 years were enrolled. Standardized questionnaires were administered to assess the patients’ levels of PSF [Fatigue Assessment Scale (FAS)], HRQoL [Short Form-36 (SF-36)], and PSD [Beck’s Depression Inventory (BDI)]. Stroke related disability was assessed by modified Rankin Scale (mRS). Responses to the SF-36 were weighted and then averaged in accordance to standard practices. FAS, BDI, and mRS scores were dichotomized and adjusted for gender. A multiple linear regression model was constructed for the HRQoL overall score. The dichotomized FAS, BDI, and mRS scores, age and gender were considered as predictors.Results: Of 100 patients enrolled (55% female), mean age = 66.7 years ± 12.8; 93% African or Caribbean American, 86% with hypertension, 53% with diabetes, and 37% with a family history of stroke/TIA. The prevalence of stroke related disability (mRS ≥ 2) was 63%, PSF (FAS≥22) was 51%, PSD (BDI ≥11) was 24%. Both PSF and PSD was seen in 20%. The cohort’s mean SF-36 score was 51.6 ± 21.1. BDI <11 was associated with a score 9.5 units higher on the SF-36 (95% CI: 2.3-16.8, p=0.01) than BDI ≥ 11; mRS <2 was associated with 19.8 units higher score on the SF-36 (95%CI: 13.7-25.8, p<0.0001) than mRS≥2. FAS score<22 was associated with 15.0 higher HRQoL score (95%CI: 8.9-21.1, p<0.0001) than FAS≥ 22. The analysis was adjusted for gender (p=0.10), while age (p=0.29) was not included. BDI, mRS, FAS, and gender accounted for 56% of the variability in the HRQoL score.Conclusion: Our results suggest that both PSF and PSD are significantly correlated with a lower HRQoL. In this minority cohort, over half of post-stroke HRQoL is attributed to depression, disability, fatigue, and female gender.