Objective: To investigate the factors associated with platelet activation in obese children. Design: Cross-sectional study. Setting: Department of Pediatrics of Regional Hospital No 1 of Mexican Institute of Social Security in Morelia, Michoaca, Mexico. Participants: 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures: Obese children (body mass index [BMI] > 85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-bese children (percentile < 85),% body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-I), lipid profile, and glucose. Results: Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (beta:0.381; t: 4.665; P=0.0001), vWF (beta:0.211; t: 2.926; P=0.004), UA (beta:0.166; t: 2.146; P=0.034), and HDL (beta:-0.215; t:-2.819; P=0.006). Conclusions: Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults.