High-level spinal cord injury (SCI) can result in spinal and supraspinal respiratory control deficits leading to insufficient ventilatory responses to exercise and training-related adaptations. We hypothesized a serotonin agonist, known to improve respiratory function in animal models, would improve adaptations to whole-body functional electrical stimulation (FES) exercise training in patients with acute high-level SCI. We identified ten patients (< 2 years of injury with SCI from C4-T3) in our program who had performed six months of FES-row training while on the Buspirone, a serotonin 1A agonist (29 ± 17 mg/day), between 2012 and 2018. We also identified well-matched individuals who trained for six months but not on Buspirone ( n = 11). A peak incremental FES-rowing exercise test and resting pulmonary function test had been performed before and after training. Those on Buspirone demonstrated greater increases in peak oxygen consumption (VO 2 peak: +0.24 ± 0.23 vs. +0.10 ± 0.13 L/min, P = 0.08) and peak ventilation (VEpeak: +6.5 ± 8.1 vs. -0.7 ± 6.9 L/min, P < 0.05) compared to control. In addition, changes in VO 2 peak and VEpeak were correlated across all patients ( r = 0.63, P< 0.01), but most strongly in those on Buspirone ( r = 0.85, P < 0.01). Furthermore, changes in respiratory function correlated to increased peak tidal volume in the Buspirone group ( r > 0.66, P < 0.05). These results suggest Buspirone improves cardiorespiratory adaptations to FES-exercise training in individuals with acute, high-level SCI. The strong association between increases in ventilatory and aerobic capacities suggests improved respiratory function is a mechanism, however controlled studies are needed to determine if this preliminary finding is reproducible.