Childhood obesity and related co-morbidities are increasing. This intervention study assessed the associations between weight changes and lipidemia in obese children and adolescents. A total of 240 obese children and adolescents (median age, 11.3 years; range, 3.9-20.9) were enrolled in a best-practice multidisciplinary chronic care treatment program. The concentrations of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TGs) and anthropometric data comprising height and weight were collected at baseline and after up to 39 months of continuous treatment. The BMI standard deviation score (SDS) decreased in 51% of patients and maintained unchanged in 32% of patients during the treatment. At baseline, 65 (27.1%) of the patients exhibited dyslipidemia defined as increased concentrations of total cholesterol (>200 mg/dL), LDL (>130 mg/dL), or TGs (>150 mg/dL), or decreased HDL concentration (<35 mg/dL). Dyslipidemia improved with weight loss; the odds ratio (OR) was 0.37 per BMI SDS (p = 0.014) after adjusting for age, sex, and baseline BMI SDS. Baseline TG concentration correlated positively and HDL concentration correlated negatively with baseline BMI SDS. Weight loss was associated with a decrease in the concentrations of total cholesterol (p = 0.0005), LDL (p < 0.0001), non-HDL (p < 0.0001), and TGs (p < 0.0001), and with an increase in HDL concentration (p < 0.0001). High lipid concentrations were associated with childhood obesity. The lipid profile improved during weight loss independently of the baseline BMI SDS and baseline lipid concentration.