Q fever is a worldwide zoonosis caused by Coxiella burnetii. The clinical manifestations of Q fever include endocarditis, pneumonitis and hepatitis. Disease awareness and evolving diagnostic tests have enabled the recognition of unusual manifestations of Q fever. We report a case of Q fever osteomyelitis. A 51-year-old patient was admitted to hospital because of fever, leg weakness, and asthenia. His past medical history included surgery and a bone graft for the treatment of a giant cell tumor on the distal part of the femur. Blood and bone biopsy cultures were negative. Bone histological examination was consistent with a sub-acute or chronic inflammatory reaction that involved foci of epithelioid and gigantocellular infiltrates and necrosis. Serology testing revealed high antibody titers to C. burnetii antigens (phase I: IgG 3200; IgA 200; phase II: IgG 6400; IgA 400), which is indicative of chronic Q fever. The specific Polymerase Chain Reaction (PCR) of the abscess sample from the femoral region was positive for C. burnetii. The patient was treated for chronic Q fever with doxycycline and hydroxychloroquine for 18 months and recovered gradually without recurrence of pain or functional impairment. Q fever osteomyelitis is a rare and most likely underestimated disease. Epithelioid and gigantocellular granulomatous osteomyelitis in the context of culture-negative bone specimens should raise suspicion of Q fever. Serological tests, specific PCR and cell culture can provide evidence of a C. burnetii infection. Although bone diffusion may be a concern, the currently recommended treatment for Q fever was effective in this case.