Summary Background A patent foramen ovale (PFO) is not widely recognized as a factor contributing to hypoxemia in patients with chronic obstructive pulmonary disease (COPD). We therefore sought to clarify the prevalence and clinical significance of a PFO in patients with COPD, and to analyze the factors related to its occurrence. Methods This study included 52 consecutive stable patients with COPD and 50 healthy controls. The demographic and clinical features of the study group were noted. To test for a PFO, standard and contrast transthoracic echocardiographic examinations were performed while resting and during the Valsalva maneuver (VM). Patients performed 6-min walking tests (6 MWT), and the distances traveled were measured. Results During VM, we detected a PFO in 23 COPD patients and 10 healthy controls ( P < 0.01 ). A PFO was detected while resting in 11 COPD patients, but in none of the controls ( P = 0.001 ). Comparison of multiple parameters between COPD patients with and without a PFO during VM did not reveal any clinically significant differences. When we compared COPD patients with and without a PFO during resting, however, we found that the former had longer durations of disease, lower PaO 2 and SaO 2, higher dyspnea scores, shorter distances walked during 6 MWT and higher desaturation rates ( P < 0.05 ). Logistic regression analysis showed that longer duration of disease, lower SaO 2 and higher systolic pulmonary artery pressure were independent predictors of the occurrence of a PFO in resting COPD patients. Conclusions The prevalence of a PFO is higher in patients with COPD than in healthy individuals. The presence of a PFO while resting may contribute significantly to the deterioration of arterial oxygenation and performance status. These findings indicate that a PFO may be a principle cause of hypoxemia in patients with COPD.