Nocardia is a Gram-positive, aerobic branched actinomycete; it is a ubiquitous soil saprophyte. Nocardia as a cause of septic arthritis is very unusual. We report a case of Nocardia cyriacigeorgica arthritis in the right knee in a 38-year-old woman who was being treated with systemic corticosteroids for systemic lupus erythematosus and was on haemodialysis. The presumptive bacterial identification of the Nocardia genus was made by Gram and acid-fast staining, growth characteristics, colonial morphology and antibiotic resistance. Identification was later confirmed by PCR and sequence determination of the 16S rRNA gene. The patient was treated successfully with trimethoprim-sulfamethoxazole for 12 months. To the best of our knowledge, this is the first detection of N. cyriacigeorgica in Tunisia and the first Tunisian report of Nocardia arthritis. This finding emphasizes the importance of optimizing conditions of bacterial isolation, especially for immunocompromised patients, to identify less common organisms and initiate early appropriate treatment.