Excessive urination can be a perioperative challenge for providers due to the possibility of secondary hypernatremia. Dexmedetomidine has previously been reported by several groups to induce a polyuric-like syndrome; however, the exact mechanism in humans remains unclear. In this report, we discuss a case of intraoperative, transient dexmedetomidine bolus-induced excessive urination and suggest a potential mechanism by which this may occur in a subset of the population.