Background: Paroxysmal sympathetic hyperactivity (PSH) is a grave entity affecting patients following traumatic brain injury (TBI). It presents with cyclic and simultaneous fever, posturing, and other symptoms of sympathetic hyperactivity. Lack of diagnostic tests or biochemical markers and its propensity to mimic other common causes of fever in the neurotrauma intensive care unit (ICU) result in clinical dilemmas and management delay. Case descriptions: We present a case series of four patients (two adults and two pediatrics) with TBI who developed PSH during ICU stay. These patients presented with fever along with variable symptoms of sympathetic hyperactivity. However, the value of serum procalcitonin (PCT) was not elevated, and management of PSH was started. Serial monitoring of PCT helped in differentiating fever due to PSH from sepsis and thus the institution of appropriate and timely treatment of PSH and also helped to use antibiotics rationally. Conclusion: The use of serum PCT in differentiating sepsis from systemic inflammatory reaction and its role in the initiation and titration of antibiotics are well described. PSH is a common entity after TBI, causing episodic fever and sympathetic hyperactivity, often confused with infectious pathology. Our report proposes the role of serum PCT in differentiating PSH from infectious etiology and management of two different clinical entities.