Hypoxia has been proposed to enhance, diminish, or have no effect on laboratory measures of coagulation or clinical thrombosis. Further, there usually are significant pathological or environmental factors concurrently present with hypoxia. Thus, the goal of the present investigation was to determine whether whole blood or plasmatic coagulation and fibrinolytic kinetics would change in response to progressive hypoxia to a systemic oxygenation (SpO2) of 70%. Healthy, conscious volunteers (n = 9) breathing a hypoxic mixture of gases during an in-vivo validation of noninvasive cerebral oximetry had blood samples collected and assessed with thrombelastography at normoxia and after SpO2 of 70%. A mild release of endogenous heparin-like activity occurred that diminished plasmatic coagulation, and a mild increase in clot lysis time also was noted. Further investigation to determine whether these phenomena occur in more chronic, less hypoxic states as sources of hypocoagulation or thrombophilia is needed.