The association between stress and cardiovascular disease (CVD) risk is becoming established. A mechanistic link clarifying the intermediate steps between the experience of stress and the development of CVD would support this association. We sought to examine the role of perceived stress as a factor associated with disturbed sleep with the goal of providing an explanation for the stress–CVD connection. We performed a cross-sectional analysis of data recorded by subjects at entry to our CVD prevention program. Data collection included questionnaire surveys, anthropometrics, and a CVD-relevant laboratory panel. Of 350 consecutively enrolled subjects (mean age 54.4 � 12.4 [SD] years, 138 men, 39%), 165 (47%) scored above the mean for stress measures. These high-stress subjects displayed an increased cardiovascular risk profile including elevated body mass index (mean � SD 31.1 � 5.9 vs. 29.0 � 5.9, r_s = 0.175), increased waist circumference (102 � 17 cm vs. 98 � 14, r_s = 0.135), and elevated high-sensitivity serum C-reactive protein (0.384 mg/dl vs. 0.356, r_s = 0.109). High-stress subjects also demonstrated greater daytime sleepiness (Epworth Sleepiness Scale: 10.4 � 5.0 vs. 7.8 � 4.8, r_s < 0.316), greater fatigue (fatigue scale: 5.4 � 2.2 vs. 3.4 � 2.4, r_s = 0.484), poorer sleep quality (Pittsburgh Sleep Quality Index: 8.5 � 4.4 vs. 5.9 � 4.0, r_s = 0.416), and shorter sleep duration (20 min less/24 h, r_s = negative 0.177) with a higher risk for sleep apnea (60% at high risk vs. 40%, p = 0.003) than low-stress subjects. High stress was associated with significant disturbances in sleep duration and sleep quality. Stress levels also correlated with daytime consequences of disturbed sleep. The stress–sleep connection may be an important mechanistic mediator of the association between stress and CVD.