OBJECTIVES: To systematically review the cost of illness and utility literature relating to systemic lupus erythematosus (SLE), and in so doing to identify and elucidate the major cost-drivers in the cost of illness of SLE. METHODS: The bibliographic databases: Medline, Embase, and NHSEED were searched on the 14th of May 2007. Health economic studies reporting data on resource-utilisation, costs and utility relating to the syndrome were included after an initial review of the abstracts of retrieved citations and a further review of the full-text publications. Furthermore, bibliographies of included studies were interrogated for additional citations. Data were extracted into predefined data extraction grids and were analysed using Microsoft Excel™. RESULTS: The search of the bibliographic databases retrieved 1182 citations. Of these, a total of 19 studies reporting cost of illness and/or utility data were included in the review. Only two studies reported both indirect and total costs, with indirect costs contributing 50.24% and 66.97% of the overall total costs of SLE. In these two studies the annual mean direct per patient cost of SLE amounted to CAN$7382 and £2613 in respective Canadian and United Kingdom populations. Of the direct costs, across all included studies reporting these data, hospitalisation was the most important cost-driver contributing between 24.6% and 56.1% of the direct costs of SLE. The systematic review also identified an absence of robust utility data, with the visual analogue scale (VAS) being the main mechanism for deriving these data. CONCLUSIONS: This review has highlighted the significant health economic impact of the disease, in terms of direct costs and productivity losses and the need for more robust utility data. Recent recommendations have defined a core set of outcomes to be included in any SLE trial programme; and from a health economic perspective these include direct and indirect costs, health-related quality of life and utilities. This review reinforces these recommendations and has identified hospitalisations and productivity losses as key cost drivers in the cost of illness of SLE.