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Neonatal lupus erythematosus (NLE) refers to a clinical spectrum of cutaneous, cardiac, and systemic abnormalities observed in newborn infants whose mothers have autoantibodies against Ro/SSA and La/SSB. The condition is rare and usually benign and self-limited but sometimes may be associated with serious sequelae. We review the pathophysiology, clinical features, and management of infants with this condition. Neonates with NLE should be managed at a tertiary care center. Multidisciplinary team involvement may also be indicated. In mothers with anti-Ro/SSA and/or anti-La/SSB antibodies and infants with congenital heart block, the risk of recurrence in subsequent offspring is 17–25%. Therefore, careful monitoring of subsequent pregnancies with serial ultrasonography and echocardiography is essential.