Background. Metabolic syndrome (MetS) and psychological distress are hypothesized to have a bidirectional relationship. According to their high prevalence in most populations, appraisal of this theory would be of great clinical and research interest. Methods. Data were available as part of the Isfahan Healthy Heart Program (IHHP). A total of 9553 men and women aged ≥19 years from three counties in central Iran were selected. Measurements consisted of serologic tests, anthropometrics, and self-reported 12-item general health questionnaire. Logistic regression analysis was used to find the association between MetS, MetS components, and distress level. Results. The mean age of 9553 participants (50% male) was 38.7 ± 15.8 years. After adjusting for demographic factors, MetS (OR = 1.25, 95% CI: 1.01-1.37), central obesity (OR = 1.40, 95% CI: 1.15-1.49), and hypertension (OR = 1.55, 95% CI: 1.42-1.70) were associated with high distress level. However, after adding smoking status and low-density lipoprotein cholesterol to the adjustment factors, hypertension (OR = 1.79, 95% CI: 1.53-1.98) and central obesity (OR = 1.41, 95% CI: 1.17-1.55), but not the MetS, remained significantly associated with distress level. Conclusion. The presence of association between the MetS as well as its key components and high distress level signifies the importance of integrating psychological assessment and intervention in the standard management of MetS patients.