This study assessed the association of cardiometabolic risk factors with systemic inflammation, insulin resistance, and adypocytokines in a Hispanic adolescent subgroup. A clinic-based sample of 101 Puerto Rican adolescents, 48 of whom were overweight or obese based on body mass index percentiles for age and sex, was recruited during 2010. Data were collected through interviews, blood pressure and anthropometric measurements, and blood drawing. Overall prevalence of the metabolic syndrome was 16.8 % and increased to 37.5 % among overweight/obese youth. The overweight/obese group exhibited significantly (p < 0.05) higher values for abdominal obesity measures, systolic blood pressure, triglycerides, insulin resistance, C peptide, high-sensitivity C reactive protein, fibrinogen, leptin, and IL-6 and lower levels of high density lipoprotein cholesterol, adiponectin, and IGF-1. Total adiponectin significantly correlated with most cardiovascular risk factors independent of sex, Tanner stage, and adiposity. Altered cardiometabolic and adipocytokine profiles were present in this Hispanic subgroup, reinforcing the need to strengthen strategies addressing childhood obesity.