Individuals with systemic lupus erythematosus (SLE) exhibit chronically elevated inflammatory markers and experience premature cardiovascular disease. Vascular dysfunction is commonly observed in SLE patients and may explain the accelerated risk. Currently it is unknown whether physical activity status influences vascular function in patients with SLE. PURPOSE: To examine macro- and micro-vascular function in sedentary and exercising SLE patients, compared with healthy controls. METHODS: A total of forty-one young and middle-aged adults, including 15 healthy controls, 12 sedentary SLE, and 14 exercising SLE patients, were studied. Macro- and micro-vascular measures included flow-mediated dilation (via ultrasonography before and after 5-min brachial occlusion), skin reactive hyperemia (via Laser Doppler), and minimal vascular resistance (via venous-occlusion plethysmography after 10-min arterial occlusion with 2-min ischemic handgrip exercise). RESULTS: Age, BMI, and metabolic risk factors were not different between the 3 groups. Maximal aerobic capacity and physical activity score were higher in exercising SLE patients compared with sedentary SLE patients. Endothelium-dependent vasodilation was lower (3.6±1.3 vs. 8.1±1.2%) and inflammatory markers (CRP, IL-12, TNF-·) were higher in sedentary SLE patients compared with healthy controls. Importantly, there were no differences in endothelium-dependent vasodilation (p=0.73) or inflammatory markers between exercising SLE patients and healthy controls. There were no differences between groups in minimal vascular resistance (a surrogate measure of resistance artery structure) or skin reactive hyperemia. In the pooled population, endothelium-dependent vasodilation was inversely associated with IL-6 and IL-10 (both p<0.05). Minimal vascular resistance was positively associated with CRP, IL-6, IL-10, and ICAM-1 (all p<0.05), and skin reactive hyperemia was inversely associated with ICAM-1, TNF- ·, and IL-10 (all p<0.05). CONCLUSIONS: Our results indicate that significant SLE-associated macro- and micro-vascular dysfunction was not observed in physically active SLE patients. Additionally, macro- and micro-vascular function was associated with inflammatory markers, suggesting that the favorable influence of physical activity may be mediated by its effect on inflammatory markers.