This study aims to determine the difference of serum Pb and Hg levels in adolescents with or without metabolic syndrome (MetS) and the association of serum levels of these heavy metals with cardiometabolic risk factors and liver enzymes in Iranian adolescents. The study population consisted of 320 adolescents (160 with MetS and 160 healthy controls). The relationship between serum heavy metals and cardiometabolic risk factors was assessed by linear regression. The odds ratios (OR) of having metabolic syndrome across Pb and Hg quartiles were determined by multiple logistic regression analysis. The mean (SD) of Pb and Hg concentrations were higher in adolescents with MetS than in those without it (0.83 (0.27) and 0.17 (0.01) vs. 0.65 (0.15) and 0.10 (0.08) μg/L, P = 0.01 and 0.0001, respectively). Increase in serum Pb and Hg was associated with increase in some cardiometabolic risk factors. Among boys and girls, diastolic blood pressure (DBP), fasting blood glucose, total cholesterol (TC), triglycerides (TG), and alanine aminotransaminase increased significantly across quartiles of serum Pb. Among girls, SBP, DBP, TC, and TG had a significant increase across Hg quartiles. The corresponding figure among boys was significant for SBP, DBP, and TG. Higher quartiles of Pb increased the risk of having MetS (OR 95 % CI 3.10, 2.25-4.27), the corresponding figure was 2.03, 1.75-3.16, across Hg quartiles. Our study showed significant associations between serum Pb and Hg levels with cardiometabolic risk factors in adolescents. In future surveys, the role of potential confounders should be considered more extensively. The clinical significance of these findings needs to be confirmed in longitudinal studies. By considering the origins of chronic diseases from early life, controlling environmental pollutants should be considered as a health priority for primordial or primary prevention of noncommunicable diseases.