Sodium disorders are common in critically ill patients with brain injury. The severity of symptoms and long-term adverse neurological outcomes are related to the degree of sodium abnormality, the time the disorder has developed, and the treatment. After severe brain trauma, hyponatremia occurs most frequently associated with cerebral salt-wasting syndrome (CSWS) or the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH). We present the case of a patient with severe brain trauma who developed CSWS, followed by a systematic review of the literature. This case report includes the clinical and laboratory criteria used for the differential diagnosis between CSWS and SIADH.