STUDY OBJECTIVES: Poor sleep and autonomic dysregulation can both disrupt metabolic processes. This study examined the individual and combined effects of poor sleep and reduced heart rate variability (HRV) on metabolic syndrome among 966 participants in the Midlife in the United States II (MIDUS II) study. METHODS: Self-reported sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI). HRV was acquired from 11-minute resting heart rate recordings. Spearman correlations, general linear regression, and logistic regression models were used to examine the study hypotheses. RESULTS: Poor sleep quality was associated with metabolic syndrome when global PSQI scores were evaluated as a continuous (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.03 to 1.11) or categorical measure (cutoff > 5, OR: 1.58, 95% CI: 1.19 to 2.10), after adjustment for confounding. There also was an association between reduced HRV and metabolic syndrome (ln [HF-HRV] OR: 0.89, 95% CI: 0.80 to 0.99; ln [LF-HRV] OR: 0.82, 95% CI: 0.72 to 0.92; ln [SDRR] OR: 0.59, 95% CI: 0.43 to 0.79; ln [RMSSD] OR: 0.75, 95% CI: 0.60 to 0.94). When the combined effects of poor sleep and low HRV were examined, the association with metabolic syndrome was further strengthened relative to those with normal sleep and HRV. CONCLUSIONS: To the best of the author\'s knowledge, this is the first study to suggest a combined effect of poor sleep and low HRV on the odds of metabolic syndrome.