There are many methods for achieving one-lung ventilation (OLV) during thoracic surgery in neonates and the accuracy of OLV may affect postoperative outcome. The authors have performed OLV using a 5 Fr Arndt endobronchial blocker (AEB, Cook Inc., Bloomington, IN, USA) on a neonate diagnosed with congenital cystic adenomatoid malformation and respiratory distress syndrome (RDS) associated with marked mediastinal shift. In spite of sufficient preoxygenation, sudden and severe fall in oxygen saturation had occurred. Since neonates with RDS may develop sudden and severe desaturation, rapid intubation with anticipation of potential difficulty is necessary as well as sufficient preoxygenation.