To assess the cross-sectional association of epicardial fat with insulin resistance, major abdominal adipose depots, and cardiovascular disease (CVD) risk factors in obese pre-pubertal and early pubertal children. By using magnetic resonance imaging in 30 pre-pubertal and early pubertal patients [21 males, Tanner Stage I-II, median age 11.2 (2.95) y, BMI z-score 2.56 ± 0.11 SDS], visceral (VAT), subcutaneous (SAT), epicardial adipose tissues (EAT) and hepatic fat fraction (HFF) were estimated. Lipid profile, liver function tests, circulating adipokines and markers of inflammation [leptin, adiponectin, tumor necrosis factors-alpha (TNF-alpha), C-reactive protein (CRP), interleukins 6 and 10 (IL-6, IL-10)] were assayed. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Body composition was measured by dual-energy X-ray absorptiometry. In 14 insulin resistant children (HOMA-IR >2.5), median values of EAT were significantly higher than in insulin sensitive mates [54.0 (35.45) cm(3) vs. 27.2 (17.03) cm(3); p = 0.03]. Moreover, EAT performed no differently in identifying insulin resistant patients (AUC 0.737; 95% CI 0.538-0.936; p = 0.028) from VAT (AUC 0.772; 95% CI 0.599-0.945; p = 0.011); SAT (AUC 0.795; 95% CI 0.628-0.0.962; p = 0.006); and HFF (AUC 0.777; 95% CI 0.607-0.947; p = 0.010). Stepwise regression analysis showed that EAT (β = 0.025; 95% CI 0.012-0.038, p = 0.001) and CRP (β = 0.622; 95% CI 0.069-0.238, p = 0.002) predicted HOMA-IR (R(2) = 0.71; p = 0.001), while VAT, SAT and HFF were excluded from the model. In pre-pubertal and early pubertal obese children, EAT is a significant marker of increased insulin resistance and associated cardiovascular risk. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.