People with spinal cord injury (SCI) are at risk of pressure ulcer development due to impaired mobility, sensation or changes in tissue properties. Increased skin temperature is one of the least explored risk factors for pressure ulcers. Since people with SCI also encounter thermoregulation deficits, investigation of the effectiveness of local skin cooling in this population is particularly important. Three groups of subjects were recruited: 1) 14 subjects with SCI at T6 and above, 2) 8 subjects with SCI below T6, and 3) 14 healthy controls. Reactive hyperemic response was the main study outcome and was measured after three different combinations of stimuli: 1) pressure only, 2) pressure with fast cooling (−4°C/min) and 3) pressure with slow cooling (−0.33°C/min). Spectral density of the skin blood flow (SBF) was used to investigate the underlying microcirculatory control mechanisms. Five of the subjects did not have reactive hyperemia in all test sessions and were excluded from statistical analysis. In the control group, the normalized peak SBF and perfusion area were close to significantly greater in pressure only as compared to fast cooling (p=0.023 and p=0.023, respectively) and slow cooling (p=0.033 and p=0.016, respectively). Although this phenomenon was not significant when analyzing subjects with SCI alone, significant changes were observed in the signal attributed to the metabolic control mechanism and were observed in this population with pressure only (p=0.019) and pressure with slow cooling (p=0.041). Since the reactive hyperemic response is mediated by different control mechanisms, the less obvious changes in reactive hyperemia in people with SCI may be due to alterations in microcirculation after injury. Results from this study suggest that local skin cooling is beneficial to ischemic tissue by decreasing the metabolic demand, and this is generally consistent with previous animal studies and our pilot study. Findings from this study also suggest that investigating time domain parameters and time-dependent spectral analysis of the SBF signal is helpful in understanding circulatory control in people with different levels of neurological deficits. This study contributes toward justification for the development of support surfaces with microclimate controls to enhance tissue integrity.