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Central nervous system melioidosis is an uncommon presentation of melioidosis infection. We report a case of a disseminated melioidosis infection with central nervous system, pulmonary, spleen, bone and cutaneous involvement in a patient with underlying systemic lupus erythematous. The diagnosis was confirmed based on positive blood and cerebrospinal fluid cultures coupled with radiological findings. Agriculture contact and underlying immunocompromised state were the predisposing risk factors for melioidosis infection in this case. Our patient was successfully treated with 10 weeks of intensive antibiotics therapy and 1 year of eradication antibiotics therapy with significant clinical and radiological improvement.