BACKGROUND & AIMS Muscle mass depletion occurring in chronic obstructive pulmonary disease still leaves questions regarding its relation with health status. How health status should be conceived and assessed is a significant obstacle in answering these questions. This study tries to appoint which domains of health status are challenged by muscle depletion and evaluates evidence of gender difference. METHODS 135 Patients enrolled in a cohort study with initial assessment of health status by the Nijmegen Integral Assessment Framework. In here 4 main domains and 16 sub-domains are recognized. These sub-domains were correlated with fat free mass index using baseline data. Associations of fat free mass and diffusion parameters with sex were elaborated. RESULTS Muscle depletion occurred predominantly in those with low body mass index, and did not correlate with sub-domains of 3 main domains: Complaints, Functional Impairment and Quality of Life. In Physiological Functioning Hyperinflation correlated weakly. Diffusion capacity significantly correlated with fat free mass index in separate analyses of pulmonary function data. Interestingly, diffusion capacity was significantly lower in women than in men. CONCLUSIONS Muscle depletion hardly affects health status in COPD. Physiological correlations, however, do exist, pointing to severe disease, especially emphysema, and female sex as important concomitant factors.