Systemic Lupus Erythematosus (SLE) is a systemic, chronic, inflammatory, autoimmune disease associated with poor physical fitness. In fact, maximal oxygen consumption (V02max) is known to be reduced in this population. This reduction is associated with disability and can partially explain the high incidence of fatigue found in SL E patients. Although V02max has bee n the focus of many investigations, the mechanisms of reduced V02max in SLE a re not fully understood. In this thesis the results of four studies are presented. In the first study (presented in two chapters), we validated two submaximal exercise tests for the prediction of V02max in SLE patients. T he use of these inexpensive and practical tests should facilitate the measurement of V02max in future epidemiological studies and clinical practice. In the second and third study, we investigated the mechanisms of reduced V02max using two different approaches. In the second study, we demonstrated for the first time that cardiac output was limiting V02max during whole body exercise. Furthermore, we demonstrated for the first time a significant reduction in a muscle endurance test which is not limited by cardiac output, suggesting that other limitations to exercise might be present. In study three and four, we specifically addressed oxygen metabolism at muscle level, a factor that could explain reduced muscle endurance. We were able to demonstrate that, during exercise, this variable is not affected in our cohort. ln conclusion, V02,nax in SLE patients with low disease activity and no organ damage is limited by cardiac output and can easily and safely be measured with submaximal exercise tests.