Pharmacological therapy can influence morbidity and mortality in severe chronic obstructive pulmonary disease (COPD). Long-term domiciliary oxygen therapy (LTOT) improves survival in COPD with chronic hypoxaemia. Oral steroid medication has been associated with improved survival in men and increased mortality in women, while inhaled steroid medication has been associated with a reduction in the exacerbation rate. We have analysed the relationships between pharmacological therapy including oxygen therapy, sex, performance status and need for hospitalization and mortality in 403 patients with COPD (201 men) after their registration in a national oxygen register for LTOT. The mean value of days spent in hospital per year was 44. An increased need of hospital care was independently predicted by a poor performance status, high age and, in women, orally administered steroid medication. Hospital admissions were significantly longer in the terminal stage of COPD among women receiving oral steroid medication. Increased mortality was predicted by a poor performance status and, in women, oral steroid treatment. Predictors of morbidity and mortality during LTOT were found to coincide. The increased mortality in women receiving oral steroid medication was found to be associated with an increased need of hospital care due to longer hospital stays during the terminal stage of the disease. When analysing effects and side-effects of steroid medication in COPD, the possibility of sex-related differences should be considered.