Individuals with hypoxic brain injury can exhibit a broad range of symptoms based on underlying etiology, severity and duration of hypoxia, course of illness, prompt and appropriate medical intervention, and more. Opioid-induced neurotoxicity may co-occur with hypoxic injury and can present as one of several specific phenotypes that have recently been identified. Resulting injury to subcortical structures including hippocampus, cerebellum, and basal ganglia can result in broad neuropsychiatric manifestations. This is the case of a 16-year-old found unresponsive after an opioid overdose. Importantly, diagnostic overshadowing can result in inappropriate attribution of symptoms of acquired brain injury of this type to primary psychiatric diagnoses, such as depression. Accurate diagnoses of neuropsychiatric symptoms in the setting of a complex neurological insult can provide access to appropriate interventions and offer better outcomes.