PURPOSE: The purpose of the present study was to test the hypothesis that cardiopulmonary baroreflex control of sympathetic vasomotor outflow is modulated by a powerful sympatho-excitatory drive from exercise pressor reflex, central command, and/or arterial chemoreflex. To test this hypothesis, under hypoxic conditions, muscle sympathetic nerve activity (MSNA) was recorded during leg cycling with an increase in central blood volume by increasing pedal frequency to increase the activity of cardiopulmonary baroreceptors. METHODS: Subjects performed mild leg cycle exercise at different pedal frequencies of 60 and 80 rpm (60EX and 80EX trials) while breathing a hypoxic gas mixture (inspired oxygen fraction = 0.12). The exercise workload of the 80EX trial was adjusted to get the same oxygen uptake as the 60EX trial. Stroke volume (SV) and cardiac output (CO) were measured non-invasively using impedance cardiology. MSNA was recorded via microneurography of the right median nerve at the elbow. RESULTS: Changes in thoracic impedance, SV, and CO in the 80EX trial were greater than those in the 60EX trial. MSNA burst frequency during hypoxic exercise in the 80EX trial (39±4 bursts/min) did not differ from that in the 60EX trial (39±3 bursts/min). CONCLUSIONS: These results suggest that a cardiopulmonary baroreflex of sympathetic vasomotor outflow during dynamic exercise is modulated by hypoxia-induced heightened sympathetic nerve activity.