A 61-year-old man presented with a 2 week history of intermittent fever, recurrent headaches, arthralgia’s and a non-pruritic erythematous macular rash on his right lower abdomen.  The patient underwent an uncomplicated lumbar puncture and was commenced on antibiotics for suspected early disseminated Lyme disease. Few hours after the first antibiotic dose he had abrupt onset of high fevers, chills, hypotension and tachycardia requiring fluid resuscitation and antipyretics. Jarisch-Herxheimer reaction (JHR) is a transient shock-like syndrome that typically follows initiation of antibiotics and is classically associated with penicillin treatment of syphilis. We discuss a patient of disseminated Lyme disease who developed JHR after commencing antibiotic therapy.