Abstract: The aim of this study was to assess the neuroprotective effects of recombinant human erythropoietin relating to mild traumatic brain injuries. Secondary stressors following mild traumatic brain injury (mTBI) are a significant source of neuronal damage. However, the temporal delay in the onset of these secondary mechanisms allows for potentially therapeutic interventions. Recombinant human erythropoietin (r-Hu-EPO) has demonstrated neuroprotective effects when administered post-injury, but neuronal survival following chronic pre-injury administration of r-Hu-EPO has yet to be described. In the present study, female Wistar rats receiving mTBI were administered r-Hu-EPO in one of two different treatment regimens. The first was a strictly therapeutic dose, administered after the injury. The second was a multi-dose regimen designed to replicate the effects of chronic r-Hu-EPO use. Control subjects received physiological saline. Morris water maze (MWM) testing revealed no significant differences between experimental groups. Contextual fear paradigms showed that the normal extinction of the fear response was absent in mTBI animals, regardless of r-Hu-Epo treatment. Histological analyses indicated that both therapeutic and chronic administration of r-Hu-EPO resulted in increased cortical neuron survival following mTBI. However, numerous side effects associated with chronic r-Hu-EPO use, but not the therapeutic dose, were noted following mTBI. These included post-injury seizure, cerebral hematoma and intracerebral hæmorrhage, among others. These findings identify a significant health risk for individuals engaging in chronic r-Hu-EPO misuse, as is the case in the large sub-population of amateur and professional athletes taking r-Hu-EPO for its performance enhancing properties.