Obesity induces a proinflammatory state and is a major cause of morbidity in the general population. However, little is known about the effects of obesity in patients with chronic inflammatory illnesses such as systemic lupus erythematosus (SLE). One hundred consecutive patients with SLE were studied to determine the relationship between body mass index (BMI) and functional capacity, measures of fatigue, quality of life, and the inflammation markers C-reactive protein (CRP), the erythrocyte sedimentation rate, and interleukin-6 (IL-6). The association between BMI and patient characteristics was determined, and multiple logistic regression models were used to adjust for age, sex, disease activity, and disease-related damage. Thirty-three patients had a normal BMI (< 25 kg/m(2)), 28 were overweight (25-29.9 kg/m(2)), and 39 were obese (> or =30 kg/m(2)). Obese patients had worse functional capacity, more fatigue, and higher concentrations of inflammation markers. The mean +/- SD modified Health Assessment Questionnaire (M-HAQ) score was 0.6 +/- 0.4 in obese patients compared with 0.3 +/- 0.4 and 0.2 +/- 0.3 in overweight patients and those with a normal BMI, respectively (P = 0.001). The mean +/- SD concentrations of CRP in obese patients (10.0 +/- 8.6 mg/liter) were higher than those in patients who were overweight (4.7 +/- 5.4 mg/liter) or had a normal BMI (6.2 +/- 9.9 mg/liter) (P < 0.001). Similarly, concentrations of IL-6 were higher in obese patients (P = 0.003). After adjusting for age, sex, disease activity, and damage indices, the associations between BMI and CRP (P < 0.001), M-HAQ scores (P = 0.005), and IL-6 concentrations (P = 0.01) remained significant. Obesity is independently associated with impaired functional capacity and inflammation markers in patients with lupus. Thus, weight loss may improve functional capacity and decrease cardiovascular risk factors.