Introduction: Brucellosis is a zoonotic infectious disease with worldwide distribution, especially in the southandcentral Americancountries, the Middle-East and the Mediterranean areas. Knee prosthesis infection due to Brucella spp. is very rare with the first casereported in 1991 and the ninth case reported in 2010. Case Presentation: Here is reported a case of a 68-year-old female patient, referring to Shafa Orthopedic hospital, Tehran, Iran, complaining about a discharge from right total knee arthroplasty. All of the knee joint aspirations and laboratory tests were negativefor infection. Initially, no clear reason was found for this painful operated knee and it was decided to revise it; however, intraoperativesamples were positive for Brucella melitensis. Unfortunately, serum indicators of Brucellosis (Wright, CoombsWright and2-mercaptoethanol (2ME) tests) had not been checked in the preoperative evaluations. After six months of antibiotic therapy forbrucellosis, a second stage revision surgery was performed successfully. Conclusions: Prosthetic infection by Brucella species is very uncommon, this is the tenth case of total knee prosthesis infection withBrucella spp. reported in the literature but all orthopedic surgeons, especially those who work in the endemic areas, should evaluatea suspected joint for brucellosis.