We present a rare case of a healthy, non-pregnant, middle-aged and immunocompetent woman who underwent laparoscopic cholecystectomy for acute cholecystitis with a post-operative course complicated by herpes simplex virus type 1 (HSV-1) hepatitis secondary to post-surgical inflammation. Her initial post-operative course was complicated by intermittent fevers, leukocytosis, jaundice, elevated transaminases, and right upper quadrant abdominal pain, and she was subsequently placed on broad-spectrum antibiotics with no improvement. During her hospital course, the patient developed herpes labialis, and HSV-1 hepatitis was confirmed by serology and HSV-1 polymerase chain reaction (PCR), in lieu of a liver biopsy. After this was discovered, the patient was placed on valacyclovir and had a successful response. The importance of this case is to emphasize the possibility of herpes simplex virus (HSV) hepatitis as a post-operative complication and the benefit of early empiric antiviral treatment.