Immunocompromised patients are at risk of developing atypical herpes simplex virus (HSV) infection, which can be easily misdiagnosed. We present a case of a 69-year-old female who was receiving methotrexate and tofacitinib for a known case of rheumatoid arthritis. She was admitted to the ICU under neurology care after presenting with status epilepticus secondary to bacterial meningitis. She complained of a group of vesicles on the erythematous base accompanied by a burning sensation, erosions with a hemorrhagic crust that extended onto the vermilion lip, and painful oral mucosa erosion that involve the buccal, palatine, and tongue. The clinical differential diagnosis was herpes simplex infection, pemphigus vulgaris, paraneoplastic pemphigus, early drug-induced Stevens-Johnson syndrome, erythema multiform major, and methotrexate-induced mucositis. As the presentation was atypical, steroid treatment was initiated. Subsequent histopathology showed infectious dermatitis consistent with herpes virus infection. After discontinuing steroid treatment and starting an antiviral drug, the patient’s symptoms improved within a week.There has been heightened clinical awareness about the atypical clinical presentation of herpes simplex infection in immunocompromised patients. HSV infection should be included in the differential diagnosis along with other vesiculobullous diseases.