Heart rate variability (HRV) is the fluctuation of the time intervals between heartbeats. The autonomic nervous system regulates HRV, and a reduced HRV won’t allow different physiological systems to properly adapt to changing environmental stimuli. In amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder that results in the death of motor neurons in the central nervous system, many physiological functions are impacted, including the autonomic nervous system. As a result, ALS can lead to a reduced HRV. Acute intermittent hypoxia (AIH) is an intervention which consists of delivering repetitive cycles of lowered oxygen followed by normoxic air and has been shown to induce cardiac and respiratory plasticity. However, it is unknown whether HRV differs as a function of AIH. The purpose of this study was to determine whether a single session of AIH altered HRV in patients with ALS and mild-moderate respiratory involvement (forced vital capacity >60% predicted). Patients and age- and gender-matched controls underwent both AIH and a sham intervention in two different sessions. AIH was delivered in 15, 1-minute bouts of 10% oxygen alternating with 2 minutes of normoxia through a face mask. The same protocol was used for the sham intervention, using only normoxic air. For various HRV metrics, recorded values were within a range considered “normal” according to previous literature measuring short-term HRV norms. HRV spectral analysis showed decreased Low-frequency bands and increased high-frequency bands in most subjects 60 minutes post-AIH (p<0.05), potentially indicating increased parasympathetic nervous system tone. The standard deviation of heartbeat intervals increased modestly in individuals with ALS after AIH (p=0.11), but not after the sham condition, suggesting AIH may promote autonomic short-term plasticity. Future studies should examine the extent to which daily AIH impacts HRV in persons with ALS and its functional significance.