Postmenopausal women experience an age-related decline in resting energy expenditure (REE), which is a risk factor for energy imbalance and metabolic disease. Exercise, because of its association with greater lean tissue mass and other factors, has the potential to mediate REE decline, but the relation between exercise and REE in postmenopausal women is not well characterized. This study tests the hypothesis that exercise energy expenditure (EEE) is positively associated with REE and can counter the effects of age and menopause. It involves a cross-sectional sample of 31 healthy postmenopausal women (aged 49-72 years) with habitual exercise volumes at or above levels consistent with current clinical recommendations. Subjects kept exercise diaries for 4 weeks that quantified exercise activity and were measured for body composition, maximal oxygen uptake, and REE. Multiple regression analysis was used to test for associations between EEE, age, body composition, and REE. There was a significant positive relation between EEE and lean tissue mass (fat-free mass and fat-free mass index). The relation between REE and EEE remained significant even after controlling for lean tissue mass. These results support the hypothesis that exercise is positively associated with REE and can counter the negative effects of age and menopause. They also indicate a continuous relation between exercise and REE across ranges of exercise, from moderate to high. Exercise at levels that are at or above current clinical guidelines might, in part, ameliorate the risk for energy imbalance and metabolic disease because of its positive relation with REE.