OBJECTIVES: Fatigue is a common symptom of systemic lupus erythematosus (SLE). Our objective was to validate the 13-item FACIT-Fatigue scale in SLE patients. METHODS: The FACIT-Fatigue scale, Brief Pain Inventory (BPI) and Patient Global Assessment Visual Analog Scale (PGA) were completed at baseline and weeks 12, 24, and 52 by patients with moderately-severely active extra-renal SLE, participating in a rituximab clinical trial (EXPLORER). The SLE Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) disease activity index were completed by physicians at the same visits.   RESULTS: At baseline, 254 patients completed the FACIT-Fatigue. The mean (19.1) was substantially lower than the US average (40.1). Cronbach’s alpha was >0.95 at all visits. In cross-sectional analyses, FACIT-Fatigue differentiated between groups defined by BILAG General domain ratings; effect sizes (mean difference/SD) were generally in the 0.5-0.6 range. FACIT-Fatigue had moderate-high correlations (r=0.6-0.7) with BPI and PGA, but poor correlations with BILAG and SLEDAI total scores (r=0.24-0.29). At weeks 12, 24 and 52, patients with improved or unchanged BILAG General status compared to baseline experienced a statistically significant improvement in FACIT-Fatigue with effect sizes in the range of 0.3-0.7. Mean FACIT-Fatigue improvement was higher in patients who improved vs. remained unchanged on the BILAG General domain. FACIT-Fatigue scores remained stable for patients with worsened BILAG General domain ratings compared to baseline (effect sizes generally <0.3). Distribution and anchor-based estimates suggested a minimally important difference (MID) range of 3-6 points.   CONCLUSIONS: The FACIT-Fatigue is a valid and responsive measure of fatigue in patients with SLE. MID in SLE sample is similar to that derived previously in other populations. Since few patients experienced worsening of BILAG General status in this study, further research is warranted to evaluate the responsiveness of FACIT-Fatigue to worsening in this population.