Objective: To examine whether the psychological traits of hopelessness and depressive symptoms are related to endothelial dysfunction. Methods: Data are derived from a subsample of 434 respondents in the 2001 to 2003 Chicago Community Adult Health Study, a population-based survey designed to study the impact of psychological attributes, neighborhood environment, and socioeconomic circumstances on adults aged ≥18 years. Circulating biomarkers of endothelial dysfunction, including e-selectin, p-selectin, and soluble intercellular adhesion molecule-1 (s-ICAM1) were obtained from serum samples. Hopelessness was measured by responses to two questions, and depressive symptoms were measured by an 11-item version of the Center for Epidemiological Studies Depression scale. Multivariate regression models tested whether continuous levels of the biomarkers (natural log transformed) were associated with levels of hopelessness and depressive symptoms separately and concurrently. Results: In age-and sex-adjusted models, hopelessness showed significant positive linear associations with s-ICAM1. In contrast, there was no significant linear association between hopelessness and e-selectin and p-selectin. Adjustment for clinical risk factors, including systolic pressure, chronic health conditions, smoking, and body mass index, did not substantively alter these associations. Results from similar models for depressive symptoms did not reveal any association with the three biomarkers of endothelial dysfunction. The associations between hopelessness and e-selectin and s-ICAM1 were robust to the inclusion of adjustments for depressive symptoms. Conclusions: Negative psychosocial traits may influence cardiovascular outcomes partially through their impact on the early stages of atherosclerosis, and specific psychosocial traits, such as hopelessness, may play a more direct role in this process than overall depressive symptoms. © 2010 by the American Psychosomatic Society.