BACKGROUND It has been demonstrated that there is an increased risk of venous thromboembolism (VTE) during air travel on flights of long duration. Patients with COPD are also at increased risk of VTE, particularly during exacerbations, possibly because of a hypercoagulable state secondary to hypoxia and/or heightened systemic inflammation. We investigated the effects of hypoxia on indices of coagulation and systemic inflammation in patients with COPD. METHODS Twenty clinically stable patients with mild COPD were recruited. Patients were randomized to receive either medical air or 100% nitrogen through a 40% venturi mask at a flow rate of 10 L/min for 2 h. Blood was sampled for thrombin-antithrombin complex (TAT), prothrombin activation fragments 1 + 2 (F(1 + 2)), von Willebrand factor antigen (VWF:Ag), D-dimer, and interleukin-6 (IL-6) at baseline and after 2 h. RESULTS Patients in the hypoxia and control groups were similar in terms of age, sex, pack-years smoked, and severity of airflow obstruction. There was no difference in baseline TAT, F(1 + 2), VWF:Ag, D-dimer, or IL-6 levels between groups. In the control group, there was no change in markers of coagulation or systemic inflammation over the 2-h study. In patients who underwent hypoxic challenge, there was an increase in TAT (P < .001), F(1 + 2) (P < .01), and IL-6 (P < .01), whereas D-dimer and VWF:Ag levels were unchanged. CONCLUSIONS This study demonstrates that a 2-h hypoxic challenge in patients with COPD results in coagulation activation in conjunction with an increase in systemic inflammation.