Objective This study investigated whether combined aerobic and resistance training in older women leads to metabolic adaptation. Methods A total of 80 women (64 White individuals; BMI: 30.0 [4.4] kg/m(2); age: 64.8 [3.5] years) followed 32 weeks of aerobic and resistance training. Body weight/composition (dual-energy X-ray absorptiometry) and resting metabolic rate (RMR; indirect calorimetry) were measured at baseline, week 16, and week 32. Metabolic adaptation was defined as significantly lower measured versus predicted RMR. A regression model to predict metabolic adaptation was developed that included race, age, baseline fat-free mass, RMR and respiratory quotient, and changes in net submaximal oxygen consumption after different tasks. Results There was significant metabolic adaptation at week 16 (-59 [136] kcal/d, p = 0.002), following a 640-kcal/wk energy loss (-0.7 [2.6] kg of weight loss). In 53 women with complete data, metabolic adaptation was seen both at week 16 (-64 [129] kcal/d, p = 0.001) and at week 32 (-94 [127] kcal/d, p < 0.001). Metabolic adaptation at week 16 was predicted by race, age, baseline fat-free mass, RMR and respiratory quotient, and change in net oxygen consumption of walking (R-2 adjusted = 0.90, p < 0.001). Similar results were seen at week 32. Conclusions In older women with overweight and obesity, a minimal energy deficit induced by aerobic and resistance exercise is associated with metabolic adaptation at the level of RMR.