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Perinatal exposure to opioids might result in opioid intoxication in a newborn infant. The routine use of naloxone in an opioid-exposed newborn infant is discouraged due to the risks of precipitating withdrawal and long-term developmental problems associated with naloxone. We describe a case of respiratory and neurological depression in an infant with intrauterine growth restriction (IUGR) following in utero exposure to an opioid two hours before delivery. The infant was apneic with a poor tone immediately after birth. With positive pressure ventilation, the tone and respiratory effort improved, and the baby was admitted to the neonatal intensive care unit (NICU) on oxygen support via nasal cannula. The baby started having bradypnea with shallow breathing and oxygen desaturation at eight hours of life, most likely secondary to intrauterine exposure to hydromorphone which was successfully reversed with a single dose of intravenous naloxone. The infant was discharged on day of life seven with no further symptoms. Naloxone administration might be considered in an IUGR infant with persistent cardiorespiratory and neurological depression who has a history of intrauterine opioid exposure within four hours before delivery provided the mother is not narcotic dependent., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Timalsina et al.)