Lifestyle intervention programs currently emphasize weight loss secondary to obesity as the primary determinant of phenotypic changes. We examined whether the effects of a short-term lifestyle intervention program differs in normal weight vs. overweight/obese children. 19 overweight/obese (O, BMI=33.6±1.9 kg/m²) and 14 normal weight (N, BMI=19.9±1.5 kg/m²) children participated in a 2-week program consisting of an ad libitum high-fiber, low-fat diet and daily exercise (2-2.5 hr). Fasting serum samples were taken pre- and post-intervention for determination of lipids, glucose homeostasis, inflammatory cytokines, and adipokines. Only O lost weight (3.9%), but remained overweight/obese (32.3±1.9 kg/m2). Both groups exhibited significant intervention-induced decreases (p<0.05) in serum insulin (N: 52.5% vs. O: 28.1%, between-group p=0.38), homeostatic model assessment for insulin resistance (N: 53.1% vs. O: 28.4%, p=0.43), leptin (N: 69.3% vs. O: 44.1%, p=0.10), amylin (N: 28.7% vs. O: 26.1%, p=0.80), resistin (N: 40.0% vs. O: 35.1%, p=0.99), plasminogen activator-inhibitor-1 (N: 30.8% vs. O: 25.6%, p=0.59), interleukin (IL)-6 (N: 58.8% vs. O: 48.5%, p=0.78), IL-8 (N: 46.0% vs. O: 42.2%, p=0.49), and tumor necrosis factor-α (N: 45.8% vs. O: 40.8%, p=0.99). No associations between indices of weight change and phenotypic changes were noted. A short-term, intensive lifestyle modification program is effective in ameliorating metabolic risk factors in normal weight and overweight/obese children. These results suggest that obesity per se was not the primary driver of the phenotypes noted and dietary intake and physical inactivity induce the phenotypic abnormalities. These data may have implications for the weight-loss independent management of cardiometabolic risk in pediatric populations.