Herpes simplex virus (HSV) are challenging etiologic agents with a wide range of clinical manifestations. We present a case of a 34-year-old immunocompetent male who was brought to the Emergency Department (ED) with fever and prostration. In the first approach, blood tests revealed an acute hepatitis without an identified etiology. Besides the use of N-acetylcysteine, he became worst and evolved to acute liver failure and coma. HSV deoxyribonucleic acid (DNA) was identified in the cerebrospinal fluid (CSF) and blood. Although acyclovir was started on day 3, he developed cardiovascular shock with multiple organ failure and died on the 7th day of hospitalization. A high index of suspicion is needed, and early diagnosis should be promoted between clinicians.