Background: Decentralization of the sympathetic nervous system in persons with spinal cord injury (SCI) results in impaired vasomotor and sudomotor activity and, subsequently, impaired thermoregulatory capacity during exercise in the heat. Hyperthermia can be life-threatening and, as such, cooling interventions are needed to prevent this sequela. Objectives: To measure change in core temperature (ΔTC) over time during exercise in normothermic and high ambient heat conditions to compare thermoregulatory capacity in persons with varying degrees of intact vasomotor and sudomotor activity and to determine the efficacy of three cooling interventions in mitigating TC rise. Methods: Three persons participated: a 51-year-old with complete (AIS A) tetraplegia (TP), a... 32-year-old with AIS A paraplegia (PP), and a 40-year-old without SCI (AB). Each exercised for 30 minutes on a wheelchair treadmill propelled at 30 revolutions per minute under five different conditions: (1) cool (C) = 75°F without cooling, (2) hot (H) = 90°F without cooling, (3) 90°F with cooling vest (CV), (4) 90°F with water spray (WS), and (5) 90°F with ice slurry ingestion (IS). ΔTC was compared for all conditions in all participants. Results: ΔTC in the C and H conditions was proportional to the neurological level of injury, with Tc rising highest in the TP followed by the PP then AB. WS was most efficacious at mitigating rise in TC followed by IS and CV in TP and PP. None of the cooling interventions provided an added TC cooling effect in AB. Conclusion: WS was most efficacious at mitigating rise in TC in TP>PP during exercise in the heat and should be studied in a larger SCI population.