The Nocturnal Oxygen Therapy Trial (NOTT) showed previously that patients with hypoxemic chronic obstructive pulmonary disease (COPD) frequently suffered from neuropsychologic deficit and experienced disturbed mood, personality, and life quality. The present study has followed up 150 NOTT patients six months after they were randomized to continuous oxygen treatment (COT) or nocturnal oxygen treatment (NOT). Tested off oxygen, 42% showed modest neuropsychologic improvement after six months of therapy, and the rates for COT and NOT were comparable. A subsample (n = 37) was examined a third time, after 12 months of treatment. At this point patients receiving COT registered better neuropsychologic performance than those receiving NOT. Concurrently, the COT group began showing improved survival. Despite mild neuropsychologic improvement, patients reported little change in emotional status or life quality. It is concluded that prolonged oxygen treatment is associated with small but definite improvement in brain functioning among patients with hypoxemic COPD, and that COT might have some advantage over NOT in enhancing neuropsychologic functioning as well as survival.