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Introduction: Rabies is a universally fatal zoonotic disease once clinical symptoms manifest. While direct human-to-human transmission is exceedingly rare, mainly reported in organ transplant recipients, the management of healthcare worker (HCW) exposure to a patient with confirmed rabies presents complex occupational and institutional challenges. We describe an ICU-based exposure event and subsequent public health response involving post-exposure prophylaxis (PEP) decisions in a tertiary community hospital. Methods: Following laboratory confirmation of rabies in a critically ill patient, a retrospective review was conducted to assess potential staff exposures. Procedural logs, ICU bedside documentation, and direct interviews were used to identify HCWs with contact involving saliva, mucous membranes, or non-intact skin. Risk stratification and PEP recommendations were developed in collaboration with local health authorities and the CDC. Data on exposure types, personnel affected, and prophylaxis administered were collected and reviewed. Results: The index case involved a 60-year-old woman with progressive encephalopathy who required intubation, neuromuscular blockade, continuous renal replacement therapy, and frequent hands-on care. Rabies virus was confirmed via PCR testing of saliva and CSF, along with fluorescent antibody staining of a nuchal skin biopsy. Over 100 HCWs were identified as potentially exposed during aerosol-generating procedures and routine ICU care. Fifteen were deemed at elevated risk and offered rabies vaccine; nine also received rabies immune globulin (RIG). RIG administration prompted institutional debate due to its unclear benefit in vaccinated, immunocompetent adults, high cost, and global supply limitations. No secondary infections occurred. Conclusions: This case illustrates the real-world complexity of managing possible rabies exposure in a modern ICU. Despite limited transmission risk, high viral shedding, and routine contact with secretions, a structured approach is necessary. Clear national guidelines, particularly regarding RIG use, are needed to support risk-based decisions, protect frontline staff, and preserve critical biologic resources.