Thrombocytopenia is a common clinical condition associated with a wide variety of clinical conditions including infections, malignancy, medications, liver disorder, and autoimmune conditions, etc. The association between thrombocytopenia and herpes simplex virus (HSV) is reported only once in a case report dating back to 1978. We report a case of a 66-year-old female with generalized weakness, mechanical fall, genital ulcerations, and breast fold and genital area skin redness, warmth, and mild tenderness. Initial labs showed mild leukocytosis, normal platelet count, mild lactic acidosis, and urine analysis suggestive of urinary tract infection. The patient was started on broad-spectrum antibiotics. During the course of hospitalization, the patient developed severe thrombocytopenia with platelet counts dropping less than 40000/μL (normal range: 150,000-450,000/μL), and genital pain and ulceration worsened. The genital swab was sent which came back positive for the HSV-2 virus. Soon after the start of acyclovir for HSV-2 infection, the genital pain and ulceration improved and platelet counts gradually increased to 157,000/μL. Other causes of thrombocytopenia such as sepsis, heparin-induced thrombocytopenia, consumptive coagulopathy, medication-induced thrombocytopenia, immune thrombocytopenia, and thrombotic thrombocytopenic purpura were ruled out.