The purpose of this study was to investigate the effects of two different aspects of compliance with liquid oxygen (LOX) therapy on quality of life and to explore possible pulmonary and psychosocial concomitants. The study sample consisted of 57 oxygen-dependent patients with chronic obstructive pulmonary disease under LOX therapy. Compliance was defined as continuous oxygen use as prescribed and also as readiness to use LOX outdoors. The study design encompassed three major measuring points, the first of which was an initial assessment, the second 3 months later and the third follow-up after 14 months. Furthermore, during the course of the study, two telephone interviews were conducted. The psychosocial variables studied included quality of life, psychological adjustment and two different aspects of compliance with LOX therapy. Seven (12%) patients used LOX less than prescribed and 13 (23%) refused to use LOX away from home. Those patients who used LOX insufficiently had a significantly lower life-satisfaction than those who were compliant (p = 0.02). The discriminance analysis included several psychosocial variables discriminating between both groups, allowing the correct classification of 85% of the patients who used LOX as prescribed and 83% of the noncompliant patients (p = 0.01). At follow-up, the data of 25 patients were available. Of these, five refused outdoor LOX use. Their quality of life was significantly worse in almost all areas examined as compared to the outdoor LOX-users (p < 0.05, respectively). Compliance is an essential prerequisite for the beneficial effects of liquid oxygen on quality of life. Because psychological factors influence adherence to liquid oxygen therapy, patients should receive individual psychological counselling and training before transfer to liquid oxygen therapy.