Ondansetron is commonly used during the peri-operative period for the prophylaxis of postoperative nausea and vomiting (PONV). It is a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. Although relatively safe, few cases of ondansetron-induced bradycardia are described in the literature. Here, we present the case of a 41-year-old female with a burst fracture of the lumbar (L2) vertebrae following a fall from height. The patient underwent spinal fixation in the prone position. The intra-operative period was otherwise uneventful, except for an unprecedented incidence of bradycardia and hypotension following administration of intravenous (IV) ondansetron, at the time of closure of the surgical wound site. It was managed with IV atropine and fluid bolus. The patient was shifted to a intensive care unit (ICU) postoperatively. The postoperative period was uneventful, and the patient was discharged in good health on postoperative day three.