Shift work, which imposes a habitual disruption in the circadian system, has been linked to increased incidence of cardiometabolic diseases, and acute circadian misalignment alters various metabolic processes. However, it remains unclear whether day-to-day circadian dysregulation contributes to these risks beyond poor sleep and other behavioral characteristics.Individuals differ in circadian phase preference, known as chronotype, but may be constrained by modern work obligations to specific sleep schedules. Individuals experience social jetlag (SJL) due to a habitual discrepancy between their endogenous circadian rhythm and actual sleep times imposed by social obligations. Here, we examined whether chronotype and/or SJL associate with components of cardiovascular disease risk beyond the known effects of sleep disturbances, poor health behaviors, and depressive symptomatology.Participants were healthy, midlife adults who worked part- or full-time day shifts (n = 447; mean age, 42.7 [range, 30-54] y; 53% female; 83% white). Chronotype was assessed with the Composite Scale of Morningness. SJL was quantified as the difference (in minutes) between the midpoints of actigraphy-derived sleep intervals before work vs non-workdays.Multiple regression analyses showed that SJL related to a lower high-density lipoprotein-cholesterol level, higher triglycerides, higher fasting plasma insulin, insulin resistance, and adiposity (P < .05), even after adjustment for subjective sleep quality, actigraphy-derived sleep characteristics, depressive symptomatology, and health behaviors. Evening chronotype associated with lower high-density lipoprotein-cholesterol after adjustment for covariates.Our findings suggest that a misalignment of sleep timing is associated with metabolic risk factors that predispose to diabetes and atherosclerotic cardiovascular disease.