While the effects of instantaneous, single-bout exposure to hypoxia have been well researched, little is known about the autonomic response during, or as an adaptation to, repeated intermittent hypoxic exposure (IHE) in a sedentary population. Resting heart rate variability (HRV) and exercise capacity was assessed in 16 participants (8 receiving IHE, [Hyp] and 8 receiving a placebo treatment [C]) before and after a 4-week IHE intervention. Heart rate variability was also measured during an IHE session in the last week of the intervention. Post-intervention, the root mean squared successive difference (rMSSD) increased substantially in Hyp (71.6 ± 52.5%, mean change ± 90% confidence limits) compared to C suggesting an increase in vagal outflow. However, aside from a likely decrease in submaximal exercise heart rate in the Hyp group (-5.0 ± 6.4%) there was little evidence of improved exercise capacity. During the week 4 IHE measurement, HRV decreased during the hypoxic exposure (reduced R-R interval: -7.5 ± 3.2%; and rMSSD: -24.7 ± 17.3%) suggesting a decrease in the relative contribution of vagal activity. In summary, while 4 weeks of IHE is unlikely to improve maximal exercise capacity, it may be a useful means of increasing HRV in people unable to exercise.Keywords: autonomic nervous system, sedentary lifestyle, interval hypoxia, simulated altitude, physical fitness, health Heart rate variability (HRV) is the analysis of the variation in the beat to beat intervals in the heart rhythm, which reflects the autonomic nervous system (ANS) innervation on the sinus node (25). Heart rate variability is also responsive to the changes in the ANS associated with external stimuli such as real or simulated altitude (21). For example, an initially sharp increase in sympathetic activity is observed upon arrival at altitude (7, 28), which gradually declines through the acclimatization process (14, 23). The reduction in HRV is largely due to a reduction in the parasympathetic drive at the sinus node during hypoxia, the mechanism behind which has been well described by Roche et al. (20). The recovery of HRV to baseline levels upon return to normoxic ambient air depends on the length and severity of the initial exposure. That is, after 12 hours of continuous hypoxic exposure, a pronounced (dampened) effect on HRV is still evident an hour after returning to normoxic ambient air (7), but after a brief hypoxic exposure of 15 min, recovery is almost immediate (20).