Pleural effusion is an extremely rare complication in neonates after umbilical venous catheterization that can present with respiratory distress, a neonatal emergency. It needs timely intervention to reduce respiratory distress. We report an interesting and rare case where a term newborn developed right-sided pleural effusion after umbilical venous catheter (UVC) insertion and starting on total parenteral nutrition (TPN). Pleural effusion was confirmed by X-ray and ultrasound and treated with intercostal drainage. The aspirated fluid was TPN, as evidenced by pleural fluid analysis. Pleural effusion resolved after removing the UVC.