BACKGROUND: Survival studies have consistently shown significantly greater mortality rates in underweight and normal-weight patients with chronic obstructive pulmonary disease (COPD) than in overweight and obese COPD patients. OBJECTIVE: To compare the contributions of low fat-free mass and low fat mass to mortality, we assessed the association between body composition and mortality in COPD. DESIGN: We studied 412 patients with moderate-to-severe COPD [Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stages II-IV, forced expiratory volume in 1 s of 36 +/- 14% of predicted (range: 19-70%). Body composition was assessed by using single-frequency bioelectrical impedance. Body mass index, fat-free mass index, fat mass index, and skeletal muscle index were calculated and related to recently developed reference values. COPD patients were stratified into defined categories of tissue-depletion pattern. Overall mortality was assessed at the end of follow-up. RESULTS: Semistarvation and muscle atrophy were equally distributed among disease stages, but the highest prevalence of cachexia was seen in GOLD stage IV. Forty-six percent of the patients (n = 189) died during a maximum follow-up of 5 y. Cox regression models, with and without adjustment for disease severity, showed that fat-free mass index (relative risk: 0.90; 95% CI: 0.84, 0.96; P = 0.003) was an independent predictor of survival, but fat mass index was not. Kaplan-Meier and Cox regression plots for cachexia and muscle atrophy did not differ significantly. CONCLUSIONS: Fat-free mass is an independent predictor of mortality irrespective of fat mass. This study supports the inclusion of body-composition assessment as a systemic marker of disease severity in COPD staging.