Many patients with chronic illnesses suffer from clinical depression (with percentages reported by clinical studies ranging from 15 to 60); even depression is more common in people with chronic medical illnesses, (e.g. Systemic Lupus Erythematosus) than in the general population. However, not every patient with a chronic illness suffers from depression. It is well known that some people think the persons who suffer from a chronic illness have a reason to be depressed, so, there is no need to go to a psychiatrist for treatment. The fact is that not only the medical condition can be the cause for depression and, not always, the treatment for a medical illness can supply the treatment for depression. The condition of clinical depression, associated with a chronic illness, needs to be early diagnosed and early treated because it can worsen the medical state. Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune disease, which affects many organs and systems. The link between lupus and depression is controversial but it is known that negative life events, lupus activity and the treatment for disease may be capable of contributing to clinical depression. We present the case of a young woman who was diagnosed with Systemic Lupus Erythematosus and who initially presented in the psychiatric department for depressive symptoms. The case raised problems in terms of diagnosis, treatment, etiology and prognosis.