OBJECTIVE: Brain dysfunction at high altitudes can be caused by both high altitude cerebral edema (HACE) and hyponatremic encephalopathy. Differentiating them is important for proper treatment but can be difficult. We present a case series of 11 patients with hyponatremic encephalopathy, all initially misdiagnosed as HACE, and we discuss key signs and symptoms that will help clinicians differentiate the 2 pathologies. METHODS: We compiled 11 cases of patients with severe hyponatremia who were diagnosed with HACE, verified through direct patient care or referral consultation. RESULTS: Patients included 5 males and 6 females aged 19 to 65 y, exercising between 2100 and 4300 m. Serum Na CONCLUSIONS: Severe hyponatremia should be considered in persons with encephalopathy at high altitudes. Although there is no established causal link between hypobaric hypoxia and hyponatremia, the potential for high altitude exposure to exacerbate exercise-associated hyponatremia warrants further investigation because the consequences of developing or misdiagnosing this process may be severe.