Neonatal lupus is a rare entity, secondary to placental transfer of antibodies from mothers with immune-mediated conditions. While pulmonary involvement is common in lupus, its incidence in neonates is extremely rare, with very few cases being reported in the literature. The authors report a case of a neonate whose mother was diagnosed with systemic lupus erythematosus, with a prenatal diagnosis of third-degree atrioventricular block. While initially admitted in the neonatal intensive care unit with no need for organ support, he presented progressive respiratory failure, initially attributed to sepsis. Favorable clinical progression after pacemaker placement allowed ventilatory weaning, but respiratory failure was again apparent. Chest computer tomography revealed areas of ground-glass lesions, raising the suspicion for lupus pneumonitis. He was started on immunoglobulin and corticosteroids, with clinical improvement. The authors consider this case to be relevant due to the rarity of acute lupus pneumonitis in neonates, alerting that it must be considered a differential diagnosis in neonates with prolonged ventilator dependency.