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Introduction: We report a case of a female neonate who developed respiratory depression following the unintentional administration of methylergonovine. The respiratory depression appeared to improve after the administration of bag mask ventilation, stimulation, and naloxone; and the baby was able to be managed without endotracheal intubation and prolonged positive-pressure ventilation., Case: A full-term female neonate was delivered vaginally without issue. Approximately 10 min after delivery, the infant was inadvertently administered 0.1 mg of methylergonovine intramuscularly instead of vitamin K. Thirty minutes later the child developed cyanotic extremities and respiratory depression with an oxygen saturation of 75%. Naloxone, 0.4 mg IM, was recommended to mitigate respiratory depression. Within 5 min the patient's respirations improved to 40 breaths per minute, cyanosis improved, and she began resisting ventilations and crying loudly. The child continued to improve and was back to baseline that evening., Discussion: Methylergonovine toxicity in neonates has been commonly associated with respiratory depression necessitating ventilatory support. In consideration of chemical structural similarity between methylergonovine and morphine, as well as signs/symptoms consistent with opioid-induced respiratory depression, naloxone was suggested., Conclusion: It appears that naloxone may reverse methylergonovine toxicity in neonates. The identification of a safe and potentially useful antidote to mitigate respiratory depression, potentially avoiding the need for intubation and more invasive interventions in this patient population is important.