Abstract Although several functional magnetic resonance imaging (fMRI) studies have been conducted in human models of mild traumatic brain injury (mTBI), to date no studies have explicitly examined how injury may differentially affect both the positive phase of the hemodynamic response function (HRF) as well as the post-stimulus undershoot (PSU). Animal models suggest that the acute and semi-acute stages of mTBI are associated with significant disruptions in metabolism and to the microvasculature, both of which could impact on the HRF. Therefore, fMRI data were collected on a cohort of 30 semi-acute patients with mTBI (16 males; 27.83±9.97 years old; 13.00±2.18 years of education) and 30 carefully matched healthy controls (HC; 16 males; 27.17±10.08 years old; 13.37±2.31 years of education) during a simple sensory-motor task. Patients reported increased cognitive, somatic, and emotional symptoms relative to controls, although no group differences were detected on traditional neuropsychological examination. There were also no differences between patients with mTBI and controls on fMRI data using standard analytic techniques, although mTBI exhibited a greater volume of activation during the task qualitatively. A significant Group×Time interaction was observed in the right supramarginal gyrus, bilateral primary and secondary visual cortex, and the right parahippocampal gyrus. The interaction was the result of an earlier time-to-peak and positive magnitude shift throughout the estimated HRF in patients with mTBI relative to HC. This difference in HRF shape combined with the greater volume of activated tissue may be indicative of a potential compensatory mechanism to injury. The current study demonstrates that direct examination and modeling of HRF characteristics beyond magnitude may provide additional information about underlying neuropathology that is not available with more standard fMRI analyses.