Background: Although the mechanisms remain unclear, depression and mental stress are associated with endothelial dysfunction and increases risk of cardiovascular disease (CVD). Recent studies suggest that circulating endothelial progenitor cells (EPC) play an important role in endothelial repair and correlate with endothelial function. Methods: We studied the relationship between the level of circulating CD34/KDR(+) EPCs and CD133/KDR(+) EPCs, brachial artery flow-mediated dilation (FMD), Depression Anxiety Stress Scales in 129 normal individuals (54 +/- 10 years, 54 men) without prior CVD or diabetes. Results: Their median depression score (DS) and stress score (SS) was 4 (range 0-34) and 6 (range 0-32), respectively. As defined by the >= 75th percentile, 41 subjects (32%) had high DS >= 8) and 31 (24%) had high SS (>= 14). Subjects with high DS had significantly lower FMD (5.4 +/- 2.7 versus 8.0 +/- 4.0%, P < 0.001) and percentage of CD34/KDR(+) EPC (1.2 +/- 1.3 versus 2.0 +/- 2.4%, P = 0.037), but not CD133/KDR(+) EPC (0.56 +/- 0.42 versus 0.68 +/- 0.76%, P = 0.44), than those with normal DS. In contrast, there were no significant difference in FMD (6.8 +/- 3.5 versus 7.3 +/- 3.9%, P = 0.46), percentages of circulating CD34/KDR(+) EPC (1.20 +/- 1.28 versus 1.95 +/- 2.34%, P = 0.052) and CD133/KDR(+) EPC (0.55 +/- 0.41 versus 0.67 +/- 0.73%, P = 0.52) between subjects with high and normal SS. Multivariate regression analyst's revealed that high DS (OR 1.08, 95% CI: 1.02-1.15, P = 0.010) and old age (OR 1.05, 95% CI: 1.01-1.10, P = 0.019), but not SS or percentage of circulating EPC, were independent predictors for decreased FMD. Conclusions: Our results demonstrated that, in subjects without significant CVD, a high DS was associated with impaired brachial FMD and depletion of circulating EPC. However, only DS, but not SS or EPC count, was an independent predictor for impaired brachial FMD. Depression and Anxiety 28:719-727, 2011. (C) 2011 Wiley-Liss, Inc.