BACKGROUND Umbilical venous catheter (UVC) insertion is a standard of care in neonatal units. Pericardial effusion, one of the rare but fatal complications of UVC insertion, requires rapid diagnosis and management, and saline contrast echocardiography may enable effective diagnosis. Here, we have reported on the case of pericardial effusion after UVC insertion, highlighted the use of saline contrast echocardiography as a diagnostic tool, and reviewed the available literature on this infrequent life-threatening complication. CASE REPORT A 31-week-old preterm male infant developed a life-threatening cardiac tamponade 1 day after UVC insertion. Pericardiocentesis was performed, and saline contrast echocardiography confirmed the diagnosis. CONCLUSIONS We concluded that pericardial effusion and tamponade should be considered in neonates with a central line who develop sudden and unexplained deterioration. Saline contrast echocardiography can confirm the optimal position of central lines and diagnose pericardial effusion related to UVC insertion.