We have previously reported an apparently paradoxical association between medical care related factors and an increased risk of chronic obstructive pulmonary disease (COPD) re-hospitalisation, in a cohort of 346 COPD subjects from Barcelona, Spain. Confounding by severity or by indication is a plausible explanation. We tested the confounding effect of severity-related variables on these paradoxical associations. Forced expiratory volume in one second (FEV1), arterial oxygen pressure (PO2) and previous COPD admissions were associated with: (1) the presence of medical care related factors, and (2) re-admission during follow-up. Risks of readmission associated with most of the medical care related factors were reduced after adjustment for the severity variables. The risk associated with long-term oxygen therapy use changed from a crude OR of 2.36 (95% CI: 1.79-3.11) to an adjusted OR of 1.38 (0.95-2.00), while that associated with anticholinergics use varied from 3.52 (2.37-5.21) to 2.10 (1.32-3.36)). We concluded that the excess risk of COPD re-admission associated with medical care related factors might be partially due to confounding by indication. Residual confounding may still account for part of the remaining excess risk. True adverse effects of some pharmacological treatments cannot be excluded.