It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight-stable randomized controlled trial of low-fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) were randomized into a 1-year, weight-stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (DeltaMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (DeltaBF) as a covariate. In men, DeltaMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, DeltaMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for DeltaBF, all differences between groups were attenuated and no longer significant. DeltaMetS were associated with DeltaBF for both men (P < 0.0001) and women (P = 0.004). After adjustment for DeltaBF, low-fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low-fat diet and/or increased physical activity appears to be body fat loss.