Traumatic brain injury (TBI) is known to inflict significant morbidity and mortality worldwide. In severe TBI cases, the resulting physical and cognitive impairments incur high management and rehabilitation costs that crucially involve monitoring intracranial pressure (ICP) and improving brain oxygenation. Normobaric Hyperoxia Treatment (NBOT) is a therapeutic strategy to improve brain oxygen metabolism and to decrease ICP by reducing tissue swelling and deactivating toxin. NBOT is administered by increasing the inspired oxygen concentration to 100% in normal atmospheric pressure. Previous studies involving NBOT had explored its effectiveness to salvage the TBI-related cognitive and motor deficits. However, the focus of these studies has frequently been on the cortical lesions despite the known facts that TBI often inflicts tissue damage to the subcortical areas such as the basal ganglia. There are growing evidence to support recent functional theories that implicate a pivotal role of the basal ganglia in regulating normal movements and cognition through dopamine (DA) and glutamate interaction. Thus, tissue damages leading to TBI-related motor and cognitive deficits may involve the different affected brain regions. This minireview attempts to highlight the key processes involved in the pathophysiology of severe TBI and offers insights into the role of NBOT by exploring its potential effects on the cerebral energy metabolism and gene expression patterns of dopamine receptor in a mouse model.