The finding of white matter damage on brain magnetic resonance imaging may correspond to a wide variety of etiologies. The differential diagnosis may be particularly difficultin immunocompromised patients with a specific autoimmune disease or who are receiving medications after a solid-organ transplant. Herein, we describe the case of a 22-year-old woman who developed serious neurological complications after an acute rejection of a kidney graft that she had received a few months previous to treat a systemic lupus erythematosus-related nephritis.We discuss the possible hypotheses underlying the development of acute leukoencephalopathy in this setting.