Abstract. Umbilical venous catheters (UVCs) are very commonly used in sick and preterm neonates for administration of fluids, medications and total parenteral nutrition (TPN). They are relatively easy to place and generally considered to be safe. Complications include infections, thromboembolism and events subsequent to catheter malposition and migration. Catheter migration or malposition with extravasation of parenteral fluid can lead to ascites, pericardial effusion or pleural effusion. A pleural effusion from correctly placed UVC is an extremely uncommon complication. To our knowledge, we report the second patient with the development of isolated pleural effusion from a correctly placed UVC. The diagnosis is confirmed by finding similar chemical compositions between pleural fluid and TPN. The pleural effusion resolved completely following emergency thoracentesis and did not recur following the removal of UVC. The diagnosis can potentially be delayed in view of extreme rarity. Hence this condition should be suspected as a remote possibility in any neonate with an indwelling UVC and developing respiratory distress.