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Our previous work demonstrated that core body temperature (Tcore) is typically lower in persons with tetraplegia and that limited exposure to cool temperature results in a decline in Tcore with an associated decline in cognitive performance, while a similar cool exposure in able‐bodied (AB) individuals did not affect Tcore or cognitive performance. Because of the prior observed effect of cool exposure in those with tetraplegia, the effect of heat exposure on Tcore and cognitive performance was determined in persons with higher spinal cord lesions (above T4).Fifteen persons with spinal cord injury (SCI) (C5‐T3, AIS A‐B) and 15 age and body mass index‐matched AB controls were acclimated to 27°C at baseline (BL) before being exposed to 35°C for up to 120 minutes (Heat Challenge). Tcore (rectal temperature) was continuously measured while cognitive performance was assessed at BL and at the end of Heat Challenge using Stroop Color and Word and Wechsler Adult Intelligence Scale‐Fourth Edition (WAIS‐IV) Digit Span tests. Persons with SCI were divided into two groups based on the magnitude of change in Tcore to Heat Challenge, High Responder (HR: > 0.5°C) and Low Responder (LR: <0.5°C).At BL, average Tcore was 36.7±0.43°C in HR (9 participants with C5‐T1), 37.2±0.33°C in LR (6 participants with C5‐T3), and 37.3±0.36°C in AB controls; Tcore was different between HR and AB groups (p<0.05). After Heat Challenge, Tcore was not significantly different among the three groups with Tcore increasing 0.75±0.32°C in HR, 0.27±0.16°C in LR, and −0.05±0.25°C in AB groups; the changes in Tcore after challenge were significant only in the HR and LR groups. On measures of cognitive performance, HR group had a significantly greater percent change compared to AB group in Stroop Word (19.8±13.5% vs. 5.2±13.9%; p=0.02, respectively) and WAIS‐IV Sequence (24.1±17.2% vs. −2.2±19.5%; p=0.003, respectively); no differences in cognitive performance were found between the LR and AB groups.Those persons with higher levels of SCI who had a greater rise in Tcore after a thermal challenge and a lower Tcore at BL also demonstrated improved cognitive performance. Thus, the HR group displayed a greater impairment in thermoregulation with associated increased vulnerability to exposure to extremes in ambient temperature. Because subnormal Tcore has been demonstrated to impair cognitive performance, efforts to maintain euthermia in vulnerable persons with higher levels of SCI should be considered with the use of practical and effective strategies to accomplish this objective.Support or Funding InformationVA Rehabilitation Research and Development Service, Small Projects in Rehabilitation Research (SPiRE): Federal Award Identification Number: I21RX001734