Introduction. The blood circulation of the skin is an accessible and representative vascular bed for examining the mechanisms of microcirculatory function. Endothelial function is impaired in systemic lupus erythematosus (SLE), which implies disorders in cell metabolism dependent on blood circulation; however, noninvasive monitoring of metabolism at the tissue and cell level is absent in daily clinical practice. Objective. The aim of the study was to examine changes of NADH fluorescence from the epidermis of a forearm measured with the flow mediated skin fluorescence (FMSF) technique in patients with SLE and to investigate whether they are associated with clinical manifestation of the disease. Materials and Methods. The study enrolled 36 patients with SLE and 34 healthy individuals. Changes of NADH fluorescence were measured using FMSF on the forearm in response to blocking and releasing of blood flow. The results were represented as ischemic (IR max and IR auc) and hyperemic response maximum and area under the curve (HR max and HR auc). Results. IR max, IR auc, HR max, and HR auc were all lower in patients with SLE (p<0.05) compared with controls. All four parameters were negatively correlated (p<0.05) with patient age. No difference was found in NADH fluorescence between SLE patients with malar rash, discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, renal disorder, hematologic disorder, or immunologic disorder and those without. No correlation was revealed between the SLEDAI score and NADH fluorescence. Conclusion. Changes of NADH fluorescence indicate the reduction in NADH restoration, observed especially during reperfusion, and suggest the occurrence of disorders in the microcirculation of the skin and/or at the mitochondrial level. Such changes of NADH during reperfusion in patients with SLE could be associated with their possible lower sensitivity to hypoxia and possibly with endothelial dysfunction.