With the prospect of semi-permanent and permanent habitable fixtures on the moon and Mars, the complications associated with long-term exposure to microgravity should be investigated exhaustively. Spaceflight Associated Neuro-Ocular Syndrome (SANS), a group of neurological and ocular effects resulting from prolonged exposure to microgravity, is characterized by significant fluid shifts into the cranium, namely cerebrospinal fluid and blood, and an upward shift of the brain relative to the skull. This syndrome, along with its immediate effects on visual acuity, cognitive ability, and motor function are recognized by NASA, but its effects on susceptibility to traumatic brain injury have yet to be studied. Using a biofidelic human body model (Toyota Human Model for Safety, or THuMS) along with a structural finite element analysis software (LS-Dyna), we were able to replicate the effects of microgravity on cerebral structures and subject the SANS-altered models to a variety of loading events. An unmodified THuMS model was used as a control for each injury event. Here we report that the pre-strained condition associated with an influx of CSF into the third and lateral ventricles results in an increased risk of traumatic brain injury according to four injury metrics. This data serves as a preliminary study into the effects of microgravity on susceptibility to traumatic brain injury. As the promise of creating a spacefaring society becomes more realistic, steps may be required to mitigate the effects of long-term microgravity exposure on susceptibility to traumatic brain injury.