Negative U waves in the electrocardiogram are highly specific indicators of hypertensive, valvular or ischemic heart disease. Hypokalemia, on the other hand, is usually associated with large positive U waves. In this report we present a case where a routine preoperative electrocardiogram showed large negative U waves in the chest leads. Thorough cardiac evaluation ruled out any of the listed structural or functional abnormalities. At the time of the recording, the patient had profound hypokalemia. After normalization of the serum potassium, the large negative U waves resolved. To our knowledge, this is the first reported case of negative U waves in hypokalemia. We offer a possible explanation for this unusual finding.