Fatigue and exercise intolerance in patients with systemic lupus erythematosus (SLE) may persist even when disease activity is controlled, and preload deficiency could be an overlooked cause. In this expert-led discussion, Drs. Luigi Adamo and Andrea Fava share insights from their research, highlighting diagnostic clues, the role of NT-proBNP, and emerging interventions aimed at improving quality of life. Dr. Adamo is an Associate Professor of Medicine and the Director of Cardiac Immunology, and Dr. Fava is an Assistant Professor of Medicine in the Division of Rheumatology and Director of Lupus Translational Research at Johns Hopkins Medicine.