School‐based interventions are an effective way to treat childhood obesity. The purpose of the present study was to biologically validate an established school‐based intervention designed to reduce standardised body mass index (zBMI) over a period of 12 months. This intervention focused on a subset of Mexican‐American children who were participating in a larger clinical weight loss study. Plasma samples were analysed from self‐identified Mexican‐American children (12–14 years) who were randomised to either a school‐based intervention (IN, n = 152) or self‐help control (CN, n = 69). Treatment was 4 days week(−1) of exercise (45 min day(−1)) and 1 day week(−1) of nutritional counselling for 6 months. Fasting (>8 h) blood samples were collected at baseline, 6 months (end of active intervention) and 12 months (6 months after the end of the active intervention). Plasma resistin, adiponectin and leptin concentration were measured using a multiplex assay. Separate linear mixed models and a P