With the advent of high-quality portable ultrasound machines, point-of-care ultrasound (POCUS) has gained interest as a promising diagnostic tool for patients with high altitude illness. Although POCUS is used successfully in hospital environments to detect interstitial pulmonary edema and increased intracranial pressure, the relationship between specific sonographic criteria and high altitude illness is still unclear. We report the case of a healthy 32-y-old male who developed acute respiratory distress and neurologic impairment at 4321 m while participating in a high altitude medical research expedition. We discuss the potential of POCUS to diagnose acute high altitude illness by lung ultrasound, optic nerve sheath diameter measurement, and echocardiography. Ultrasound in combination with clinical findings helped us to exclude relevant differential diagnoses, start on-site treatment, and organize an evacuation. We used serial clinical and ultrasound examinations to assess the patient over time. Although its role in high altitude medicine needs further investigation, we believe that POCUS can be a valuable tool to aid clinical decision-making in remote, high altitude environments.