OBJECTIVE Fatigue in systemic lupus erythematosus (SLE) is burdensome and must be assessed using validated scales. Although the psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in SLE have been evaluated previously, its content validity in this disease remains to be evaluated. The study objective was, therefore, to evaluate content validity of the FACIT-Fatigue in SLE. METHODS Three SLE focus groups (n=21) in the United States were conducted using semi-structured interviews. Participant comments were categorized by response type, and relative response strength was qualitatively assessed. RESULTS Participants were mostly female (90%; n=19), white (57%; n=12) with a mean age of 43.7 years (range=28-70). Most scale items were considered relevant with the exception of four items for which participant interpretations varied. Consistent with the scale's measurement model, "listless" on item 3 ("I feel listless ('washed out')") was interpreted as physical or mental impairment. Participant responses to item 8 ("I am able to do my usual activities") sometimes included influence of other health conditions, which is acceptable because it is difficult to separate disease-specific and general fatigue. Some participants found item 7 ("I have energy") irrelevant and most could not relate to item 10 ("I am too tired to eat"). However, both items were intended to capture the extreme ends of fatigue (item 7, ceiling; item 10, floor). CONCLUSIONS From a content perspective, items of the FACIT-Fatigue scale were relevant for measuring fatigue in SLE.