Exposure to low-oxygen conditions (hypoxia), as encountered at high altitudes and in some pathological conditions, results in the activation of various physiological stressors and acclimatization to hypoxia. Previous studies show that administration of a novel probiotic (SLAB51; O2BOOSTER; Hecto, Seoul, South Korea) improves oxygen saturation in severely hypoxemic COVID-19 patients and in healthy participants upon exposure to simulated and terrestrial hypobaric hypoxic. Whether SLAB51 impacts stress responses such as activation of the sympathetic nervous system during high-altitude exposure has not been evaluated. We hypothesized that SLAB51 treatment and the associated increase in oxygen saturation would reduce metrics of heart rate variability (HRV) at high altitude. Volunteers of Latino ancestry (n=17; eight women, nine men) were recruited and completed sea-level and high-altitude measurements (up to four days at the University of California White Mountain Barcroft Research Station, 12,470 ft / 3,801 m). Participants ingested either the SLAB51 probiotic or a placebo (randomized double-blind procedure) upon arrival and throughout their duration at altitude, and oxygen saturation (SpO2), electrocardiogram (EKG), mean arterial blood pressure (MABP), and heart rate (HR) measurements were collected during a fasted state each morning. We performed HRV analysis based on data from 10 minutes of resting EKG recordings, which included evaluations of low-frequency (LF) and high-frequency (HF) bands and their ratio (LF/HF) as an estimation of sympathetic activity. All values were compared between probiotic and placebo groups at high altitude (mean ± SEM). The two groups did not exhibit differences in LF/HF, MABP, and HR on any of the days spent at high altitude; however, during the first evening at high altitude when the treatment groups exhibited differences in SpO2 (separately reported), the probiotic group exhibited a non-significant trend of lower MABP relative to the placebo group (n = 5, 87.3 ± 2.5 and n = 4, 93.5 ± 3.5, respectively; p = 0.078). Additionally, higher SpO2 associated with lower MABP (R2 = 0.33) across all time points at high altitude in the probiotic group, but the opposite relationship was noted in the placebo group (R2 = 0.30). These data suggest potential differences in sympathetic nervous system activation in probiotic and placebo groups, a finding which warrants further investigation in a larger sample of individuals. SLAB51; O2BOOSTER; Hecto, Seoul, South Korea. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.