ICU admission due to serotonin syndrome (SS) is well described in the literature. However, development of SS during ICU admission has not been reported to date. We present a patient in whom SS was suspected during ICU admission. SS may be induced by either increased serotonergic activity or by lowering the cerebral serotonin sensitivity threshold. SS is not easily recognized, especially in ICU populations because it can easily be confused with clinical deterioration or other drug-related toxidromes. SS is a potentially fatal clinical syndrome, which requires rapid diagnosis and timely treatment. This case demonstrates the need to consider SS in the differential diagnosis of ICU patients with unexplained hyperthermia and signs of autonomic dysregulation, who are treated with serotonergic active medication.