A prospective study was performed to confirm the prevalence pattern of the most frequent co-morbidities and to evaluate whether characteristics of patients, specific comorbidities and increasing number of comorbidities are independently associated with poorer outcomes in a population with complex chronic obstructive pulmonary disease (COPD) submitted for pulmonary rehabilitation (PR).316 outpatients (mean¡SD age 68¡7 yrs) were studied. The outcomes recorded were comorbidities and proportion of patients with a pre-defined minimally significant change in exercise tolerance (6-min walk distance (6MWD) +54 m), breathlessness (Medical Research Council (MRC) score -1 point) and quality of life (St George's Respiratory Questionnaire -4 points).62% of patients reported comorbidities; systemic hypertension (35%), dyslipidaemia (13%), diabetes (12%) and coronary disease (11%) were the most frequent. Of these patients, .45% improved over the minimum clinically important difference in all the outcomes. In a logistic regression model, baseline 6MWD (OR 0.99, 95% CI 0.98-0.99; p50.001), MRC score (OR 12.88, 95% CI 6.89-24.00; p50.001) and arterial carbon dioxide tension (OR 1.08, 95% CI 1.00-1.15; p50.034) correlated with the proportion of patients who improved 6MWD and MRC, respectively. Presence of osteoporosis reduced the success rate in 6MWD (OR 0.28, 95% CI 0.11-0.70; p50.006).A substantial prevalence of comorbidities in COPD outpatients referred for PR was confirmed. Only the individual's disability and the presence of osteoporosis were independently associated with poorer rehabilitation outcomes.