Mediterranean spotted fever (MSF) is an emerging zoonosis caused by Rickettsia conorii. The MSF typically presents with a triad of fever, generalized cutaneous rash and inoculation eschar, but its clinical spectrum may range from a mild febrile illness to a potentially life-threatening condition, being central nervous system involvement highly rare. We report the clinical case of a 63-year-old male patient with MSF complicated by acute encephalitis and multi-organic failure.