Brucellosis is a chronic granulomatous infection and may present with various clinical manifestations. Brucellar spondylodiscitis symptoms are initially subtle and nonspecific. Annexin A2 (ANXA2) is involved in various biological functions, including osteoclast formation, bone resorption, and cell growth regulation. In this study, we aimed to determine the clinical significance of serum ANXA2 levels in acute brucellosis and brucellar spondylodiscitis. This prospective study included 96 acute brucellosis patients and 51 healthy controls. Acute brucellosis was diagnosed by a 1/160 or higher titer in a standard tube agglutination (STA) test or a four-fold increase in titers between two STA tests performed two weeks apart in the presence of clinical symptoms within the last eight weeks and/or growth of Brucella spp. in appropriately prepared culture media. ANXA2 levels were determined with an enzyme-linked immunosorbent assay (ELISA). Forty (41.7 %) of 96 acute brucellosis patients were male and 56 (58.3 %) were female. Serum ANXA2 levels were elevated in patients compared to healthy controls (p = 0.001). Eighteen of 96 (18.7 %) acute brucellosis patients had brucellar spondylodiscitis. The serum ANXA2 levels of patients with brucellar spondylodiscitis were higher than those of patients with acute disease without brucellar spondylodiscitis (p = 0.001). ANXA2, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were elevated in the brucellar spondylodiscitis group compared to patients without brucellar spondylodiscitis. Serum ANXA2 measurement together with ESR and CRP is thought to be indicative in the diagnosis of brucellar spondylodiscitis, a common complication of brucellosis.