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There is a debate over the independent effects of aerobic fitness and body fatness on mortality and disease risks.To determine whether a 25% energy deficit that produces equal change in body fatness leads to greater cardiometabolic benefits when aerobic exercise is included.Thirty-six overweight participants (16 males/20 females) (39 ± 1 yr; 82 ± 2 kg; body mass index = 27.8 ± 0.3 kg·m2, mean ± SEM) were randomized to one of three groups (n = 12 for each) for a 6-month intervention: control (CO, weight-maintenance diet), caloric restriction (CR, 25% reduction in energy intake), or caloric restriction plus aerobic exercise (CR + EX, 12.5% reduction in energy intake plus 12.5% increase in exercise energy expenditure). Food was provided during weeks 1-12 and 22-24. Changes in fat mass, visceral fat, V˙O2peak (graded treadmill test), muscular strength (isokinetic knee extension/flexion), blood lipids, blood pressure, and insulin sensitivity/secretion were compared.As expected, V˙O2peak was significantly improved after 6 months of intervention in CR + EX only (22 ± 5% vs 7 ± 5% in CR and −5 ± 3% in CO), whereas isokinetic muscular strength did not change. There was no difference in the losses of weight, fat mass, or visceral fat and changes in systolic blood pressure (BP) between the intervention groups. However, only CR + EX had a significant decrease in diastolic BP (−5 ± 3% vs −2 ± 2% in CR and −1 ± 2% in CO), in low-density lipoprotein (LDL) cholesterol (−13 ± 4% vs −6 ± 3% in CR and 2 ± 4% in CO), and a significant increase in insulin sensitivity (66 ± 22% vs 40 ± 20% in CR and 1 ± 11% in CO).Despite similar effect on fat losses, combining CR with exercise increased aerobic fitness in parallel with improved insulin sensitivity, LDL cholesterol, and diastolic BP. The results lend support for inclusion of an exercise component in weight loss programs to improve metabolic fitness.