Respiratory sinus arrhythmia (RSA) is the normal fluctuation in heart rate (HR) in phase with the respiratory cycle, increasing during inspiration and decreasing during expiration. The underlying mechanisms and potential physiological utility remain elusive. RSA magnitude is thought to be affected by autonomic balance, with sympathetic nervous system (SNS) activation attenuating its magnitude. In addition, RSA is thought to improve ventilation-perfusion (V/Q) matching in the lung, which may protect oxygen saturation in hypoxia. We hypothesized that (a) acute hypoxia would decrease the magnitude of RSA through SNS activation, and (b) those with larger RSA in hypoxia would have improved oxygen saturation. Healthy participants (n=15) were instrumented with a pneumotachometer and instructed to breathe at three percentages (30, 40 and 50%) of their forced vital capacity (FVC) at three levels of randomized inspired gases: (a) room air (21%), (b) hypoxia (~13.5%) and (c) hyperoxia (100%). RSA was quantified via the peak-valley approach, and RSA reactivity (RSAR) was quantified as the slope of increases in RSA across FVC levels. RSA magnitude was not different at each percentage of FVC with each gas (P>0.05), nor were RSAR slopes different between gases (P=0.97). There was no relationship between RSA magnitude at 50% FVC in hypoxia, and the improvement in oxygen saturation from baseline breathing (r=-0.011, P=0.71). Our data provides evidence that (a) hypoxic stimulation of the carotid bodies elicits activation of both arms of the autonomic nervous system, maintaining autonomic balance and (b) RSA magnitude plays no role in improving V̇/Q matching in hypoxia.