Umbilical Venous Catheterization (UVC) is a common practice in neonatal units, though not without risks. Complications may occur in over 20% of patients; however pleural effusion is extremely rare. We report a case of an extreme preterm male neonate weighing 810 g, who developed pleural effusion due to malpositioned UVC. Pleural fluid was biochemically similar to parenteral nutrition solution. This alongside with the absence of recurrence of pleural effusion after UVC removal, support the causality between the UVC and pleural effusion. This case emphasizes the need to confirm the correct positioning of UVC. When in doubtful position, it should be withdrawn as early as possible, ensuring an alternative central access. If the clinical situation does not allow it, it is important to consider the osmolarity of the perfused solution, due to the risk of endothelial damage.