Systemic Lupus Erythematosus (SLE) is an autoimmune, multisystem disorder with various manifestations. There are limited reports on the neuropsychiatric findings as the first manifestation of SLE in children. Herein, we report a 14-year-old Iranian boy with a two-year history of cognitive dysfunction and behavioural problems as well as a recent history of epistaxis. The patient workup ended with a diagnosis of Klinefelter's syndrome associated with juvenile SLE. Patients with Klinefelter's syndrome may exhibit behavioural problems and psychological disease. These psychiatric disorders could be complicated with lupus in children. In fact, psychiatric symptoms may occur as the first manifestation of juvenile SLE. Specially, if accompanied with Klinefelter's syndrome. We suggest the diagnosis of SLE must be considered in all children with neuropsychiatric manifestations.