Introduction: Sleep apnea-induced acute hypoxia and arterial oxygen desaturation are common phenotypes in arterial hypertension. While the transient hypoxic insult alone does not consistently elevate blood pressure, it does trigger exaggerated increases in muscle sympathetic activity (MSNA) among hypertensive individuals. Elevated resting MSNA levels correlate with greater blood pressure variability (BPV), an index associated with an increased likelihood of target organ damage regardless of absolute blood pressure levels. Hypothesis: We hypothesized that transient hypoxic insults would provoke exaggerated increases in BPV among hypertensive individuals. Additionally, hypoxia is known to reset the arterial baroreflex operating point to higher pressures. We also theorize that exaggerated increases in BPV will be followed by reduced sensitivity of the spontaneous cardiac and sympathetic arms of the baroreflex. Methods: Eight 1-2 stage naive hypertensive (HT– 43 ± 12 yrs.) and normotensive (NT – 40 ± 11 yrs.) men were exposed to 5-minute bouts of (1) normoxia (21% O₂) and (2) isocapnic-hypoxia (10% O₂). Oxygen saturation (pulse oximetry), beat-to-beat BP (photoplethysmography), MSNA (Microneurography), and partial pressure of end-tidal carbon dioxide (PETCO₂) were monitored throughout the study. PETCO₂ clamp was performed through a rebreathing system. We calculated the standard deviation (SD), average real variability (ARV), and other indices of BPV. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. Results: Independent T-tests indicated that both experimental groups showed similar reductions in oxygen saturation in response to isocapnic-hypoxia (NT −25.7 ± 3.3 vs. HT −21.2 ± 4.0%, p > 0.05). There were no substantial changes in BP absolute levels and PETCO2 during isocapnic hypoxia. MSNA recordings revealed greater increases in sympathetic activation of hypertensive individuals (HT +12.7 ± 6.7 vs. NT +3.6 ± 1.6 bursts/min, p = 0.012). Isocapnic-hypoxia similarly increased BPV (HT SD: +4.7 ± 1.6 versus NT +7.6 ± 4.4 mmHg, P = 0.006; HT +2.9 ± 1.0 versus NT +4.7 ± 1.9 mmHg, P = 0.001; HT +3.3 ± 1.1 versus NT +5.4 ± 2.7 mmHg, P = 0.002, for systolic, diastolic and mean BP, respectively) in both hypertensive and normotensive individuals. Other traditional measures of variability showed similar results. Isocapnic-hypoxia provoked similar reductions in cardiac and sympathetic baroreflex gain in both groups. Conclusion: In summary, isocapnic hypoxia increases blood pressure variability and reduces both cardiac and sympathetic baroreflex sensitivity in normotensive and hypertensive men.