Self-reported ratings of sleep quality and symptoms of poor sleep have been linked to increased risk of coronary heart disease (CHD), Type 2 diabetes and hypertension with recent evidence suggesting stronger associations in women. At this time, the mechanisms of action that underlie these gender-specific associations are incompletely defined. The current study examined whether gender moderates the relation of subjective sleep and sleep-related symptoms to indices of inflammation, coagulation, insulin resistance (IR) and psychosocial distress, factors associated with increased risk of cardiovascular and metabolic disorders. Subjects were 210 healthy men and women without a history of sleep disorders. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and frequency of sleep symptoms. In multivariate-adjusted models, overall poor sleep quality, more frequent problems falling asleep (>2 night/week) and longer periods to fall asleep (>30 min) were associated with greater psychosocial distress, higher fasting insulin, fibrinogen and inflammatory biomarkers, but only for women. The data suggest that subjective ratings of poor sleep, greater frequency of sleep-related symptoms, and longer period of time to fall asleep are associated with a mosaic of biobehavioral mechanisms in women and that these gender-specific associations have direct implications to recent observations suggesting gender differences in the association between symptoms of poor sleep and cardiovascular disease.