Sighs are augmented breaths associated with psychological or physiological stresses. They also occur periodically during normal breathing to prevent atelectasis and preserve gas exchange. Specialized medullary neural circuits integrate and increase sighing in response to conditions such as hypoxia. If these circuits are vulnerable to neurodegeneration, sighing frequency or amplitude may degrade. For example, with amyotrophic lateral sclerosis (ALS), progressive loss of alpha motor neurons will degrade the capacity to sigh. Therapeutic acute intermittent hypoxia (tAIH) is a well-characterized stimulus of respiratory motor plasticity with potential to preserve/restore breathing ability in people with ALS (and other neuromuscular disorders), but it is unknown if tAIH alters sighing behavior in humans with ALS. Thus, our objective was to evaluate whether tAIH elicits plasticity in sigh volume and/or timing in adults with ALS (n= 5; 69±4 years old; 25±3 kg/m2; 60% bulbar onset; FVC 80±21 %) and age-matched healthy adults (n= 5; 67.8±3.5 years old; 26.4 ± 4 kg/m2; FVC 104±15 %). Subjects underwent single tAIH (15 cycles, 1min 10% O2, 2min 21% O2) and sham hypoxia exposures (45 min of 21% O2) in random order, separated by one week. Sigh timing and volume, plus pre- and post-sigh breaths, were assessed during resting breathing at baseline and 60 minutes post-intervention. Two-way mixed-effects analysis was used to make statistical inferences. In ALS patients, sigh volume trended higher after tAIH, but not after sham hypoxia (Sham: Pre: 1.32 (.17) L, Post: 1.22 (.45) L; AIH: 1.37 (.52) L, Post: 1.56 (.69) L, p=0.09). No significant differences were detected in sigh timing, or in timing and volume of pre- and post-sigh breaths in either group. These preliminary findings in a small sample size suggest that resting ventilation remains stable in patients and controls, but hint at an improved ability to generate larger sigh volumes after tAIH. Facilitation of sigh-generating capacity following tAIH could potentially benefit respiratory health and warrants further study.