Fatigue, a complex symptom, significantly affects the quality of life in many patients with systemic lupus erythematosus (SLE). To understand this phenomenon, 23 patients with SLE and fatigue were studied. Standardized tests of depression (NIMH), fatigue, exercise tolerance (ETT) on a bicycle ergometer, and SLE activity were obtained. At baseline, SLE patients had significantly lower maximum oxygen consumption (Vbj max) than normals (p ≪ 0.005). Adjusted for age and sex, SLE patients perform at 54% of their expected maximum Vo2, which is similar to published data from patients with rheumatoid arthritis. Depression by NIMH was not correlated with Vo2 max or length of time on ETT. Fatigue measured by Profile of Mood States (POMS) was correlated with ETT time (r = 0.476, p ≪ 0.025) and with Vfoj max (r = −0.402, p ≪ 0.07). After an 8-week aerobic conditioning programme the experimental group increased their aerobic capacity by 19% in contrast to 8% in controls. This change correlated with decreased fatigue as measured by visual analogue scales. Exercise did not exacerbate disease, and only two of 16 experimental subjects experienced transient joint symptoms during exercise.