Artificial gravity has been proposed as a method to counteract the physiological de-conditioning of long duration spaceflight, however the effects of hypergravity on the central nervous system has had little study. The study aims to investigate whether there is a relationship between prefrontal cortex brain activity and prefrontal cortex oxygenation during exposure to hypergravity. Twelve healthy participants were selected to undergo hypergravity exposure aboard a Short Arm Human Centrifuge. Participants were exposed to hypergravity in the +Gz axis, starting from 0.6+Gz for females, and 0.8+Gz for males, gradually increasing by 0.1+Gz, until the participant showed signs of syncope. Brain cortical activity was measured using electroencephalography (EEG), and localized to the prefrontal cortex using standard low resolution brain electromagnetic tomography (LORETA). Prefrontal cortex oxygenation was measured using near-infrared spectroscopy (NIRS). Analysis of variance, including Fisher’s least significant difference post hoc test were used to determine significant changes in prefrontal cortex cortical activity and oxygenation, and Pearson’s test of correlation to determine any relationship between the two. A significant increase in prefrontal cortex activity (p < 0.05) was observed during hypergravity exposure compared to baseline. Prefrontal cortex oxygenation was significantly decreased during hypergravity exposure, with a decrease in oxyhemoglobin levels (p < 0.05) compared to baseline, and an increase in deoxyhemoglobin levels (p < 0.05) with increasing +Gz level. No significant correlation was found between prefrontal cortex activity and oxy/deoxyhemoglobin. It is concluded that the increase in prefrontal cortex activity observed during hypergravity was most likely not the result of increased +Gz values resulting in a decreased oxygenation produced through hypergravity exposure. No significant relationship between prefrontal cortex activity and oxygenation measured by NIRS, concludes brain activity during exposure to hypergravity may be difficult to measure using NIRS. Instead, the increased in prefrontal cortex activity might be attributable to psychological stress, which could pose a problem for the use of a SAHC as a countermeasure.