Objective To analyze the clinical characteristics of brucellosis cases with fever of unknown origin (FUO) as initial manifestation,and to further raise awareness of doctors in non-epidemic areas.Methods Clinical data of 19 brucellosis cases with FUO as initial manifestation in Huashan Hospital,Fudan University and Jing'an branch from June 2005 to July 2016 were collected.The epidemiological,clinical,assistant examination,imaging,treatment and prognosis data of these patients were retrospectively analyzed.Results The average age of the 19 cases was 48 years old,of whom 3 were female and 16 were male.Seventeen cases had the history of contact with sick livestock or epidemic areas.The main clinical manifestations were hepatomegaly or splenomegaly or lymphadenectasis (14 cases),bone,joint and spine involvement (9 cases),orchitis (3 cases),encephalopathy and peripheral neuropathy (1 case),infectious myelitis (1 case) and sequelae of infectious transverse myelitis (1 case).Brucella was detected in 7 patients by blood culture.The agglutination test of serum antibody were 100％ positive.All patients got improvement after anti-Brucella therapeutic regimen based on doxycycline.Conclusion Brucellosis should be considered for patients with FUO from non-epidemic areas according to clinical and epidemic features.