Background: Complications associated with central vein cannulation (CVC) in the adult and pediatric population are well known. On the contrary, adverse events following peripheral vein cannulation (PVC) are rare. Case Report: A 13 months infant was admitted to the Emergency Department for bowel obstruction and severe dehydration. A right external jugular vein access was positioned and fluid infusions started. After few hours the infant became tachypnoic, tachycardic with high lactate levels. An X-ray of the abdomen showed air-fluid levels. The infant was successfully resuscitated following cardiac arrest. A lung ultrasound and a chest X-ray showed a massive right pleural effusion. A chest tube was placed in the right pleural cavity and clear fluid under pressure was drained, which was almost the amount of fluid infused through the right PVC, with stabilization of the general condition. Conclusion: Cannulation of the external jugular vein in infants may result in severe respiratory and cardiac complications and always require adequate monitoring of the patient.