Objective Management of systemic lupus erythematosus (SLE) is complex and variability in practices exists. Guidelines have been developed to help improve the management of SLE patients, but there has been no formal evaluation of these guidelines. This study aims to compare the scope, quality, and consistency of clinical practice guidelines on the diagnosis, monitoring, and treatment of patients with SLE. Methods Electronic databases were searched up to April 2014. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and textual synthesis was used to appraise and compare recommendations. Results Nine clinical practice guidelines and 5 consensus statements were identified, which covered 7 topics: diagnosis, monitoring, treatment, neuropsychiatric SLE, lupus nephritis, antiphospholipid syndrome, and other manifestations of lupus. The methodological quality of the guidelines was variable, with the overall mean AGREE II scores ranging from 31% to 75%, out of a maximum 100%. Scores were consistently low for applicability, with only 1 guideline scoring above 50%. There was substantial variability in the treatments recommended for class II and V lupus nephritis, the recommended duration of maintenance therapy for class III/IV lupus nephritis (from 1 to 4 years), and timing of ophthalmologic examination for patients taking corticosteroids. Conclusion Published guidelines on SLE cover a complex area of clinical care, but the methodological quality, scope, and recommendations varied substantially. Collaborative and multidisciplinary efforts to develop comprehensive, high-quality evidence-based guidelines are needed to promote best treatment and health outcomes for patients with SLE.