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Isolated shoulder sepsis is an uncommon clinical problem with little information in the literature on causative organisms and potential sequelae. We examined the organisms involved, surgical treatments, antibiotic treatments rendered, and complications in these cases. We retrospectively reviewed the records of 19 adult patients (19 shoulders) who underwent operative treatment of isolated shoulder sepsis from 1996 to 2005. Patient age, gender, laboratory studies, previous treatment, surgical procedures, surgical findings, cultured organism, antibiotic treatment, and complications were reviewed. The organisms included methicillin-susceptible Staphylococcus aureus (five), Streptococcus B beta hemolytic (five), Staphylococcus epidermidis (three), negative cultures (two), Streptococcus viridans (one), Escherichia coli (one), methicillin-resistant S. aureus (one), and Propionibacterium acnes (one). We treated patients with intravenous antibiotics an average of 4.2 weeks (range, 3-8 weeks). One patient underwent humeral head resection with an antibiotic spacer. Another patient died during hospitalization. Open or arthroscopic débridement in conjunction with appropriate antibiotics appears effective in eradicating infection in most adults who present with shoulder sepsis. Functional outcome is poor in those patients with irreparable rotator cuff tears and/or cartilage loss.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.