Purpose: Carotid occlusion may result in stroke, TIA, and cognitive reductions. Whether cognition predicts quality of life (QOL) for patients with carotid occlusion is unknown. Depression is also known to affect QOL. We examined whether cognition and depression predicted QOL in patients with carotid occlusive disease who have not had revascularization. Methods: Patients with unilateral carotid occlusion and history of TIA or a remote history of minor stroke were included. Patients underwent exam of memory, language, motor, and executive function skills and completed depression and QOL questionnaires (Center for Epidemiological Studies-Depression [CES-D], Stroke Specific QOL [SSQOL]). Deficits from remote stroke were assessed with the NIH Stroke Scale (NIHSS). Z-scores for cognitive tests were averaged (Cog-Z). The SSQOL scores were averaged across subgroup domains. Analyses of patients with all depression levels were followed by subgroup analyses for patients with minimal depression. Correlation findings were used to select the variables in a regression model to predict SSQOL. Results: Among 37 patients with all depression levels, QOL was predicted by deficits from remote stroke and depression (F(3, 36) = 21.15, P<.0005; NIHSS Beta = –.392, P = .001; CES-D Beta = –.577, P < .0005). Among 22 patients with minimal depression, QOL was predicted by cognitive and depression scores, (F(2,21) = 7.88, P = .003; Cog-Z Beta = .364, P = .05; CES-D Beta = –.495, P = .01). Conclusions: In patients with carotid occlusive disease without major stroke and without revascularization, cognitive and depression scores independently predicted QOL. These data demonstrate the clinical relevance of cognitive and mood decline among patients with carotid occlusion.