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Japanese spotted fever (JSF) is an emerging acute febrile natural infectious disease caused by the neglected zoonotic pathogen Rickettsia japonica . Here we reported a 64-year-old female patient who initially presented to the local hospital with an intermittent fever of unknown origin (FUO). A systemic, evident edema and eschar on the skin of the patient's upper limb was observed. The patient was diagnosed with critical Rickettsia japonica bloodstream infection by Q-mNGS and treated with doxycycline, as well as symptomatic treatments. Unfortunately, the patient passed away as a result of complications of septic shock and multiple organ and acute respiratory failure. Delayed treatment resulting from the nonspecific clinical symptoms in the early stages of infection can lead to fatal complications. Q-mNGS is an emerging pathogen detection method with the advantages of comprehensive detection, high accuracy and sensitivity and should be promoted and applied by clinicians.