Aim and background: Urea cycle disorders (UCDs) are rare genetic metabolic conditions resulting from deficiencies in urea cycle enzymes, which lead to hyperammonemia. In cases of partial enzyme deficiencies, symptoms may not emerge until adulthood, often triggered by stress, illness, or pregnancy. Pregnancy exacerbates these challenges, as the peri-partum catabolic state can precipitate hyperammonemic crises. This report describes a case of isolated hyperammonemia in a postpartum patient due to urea cycle enzyme deficiency. Case description: A 24-year-old primigravida presented with disorientation and somnolence on the fourth postoperative day after a cesarean section. Her history revealed decreased mentation and vision since childhood. Laboratory tests were normal except for elevated serum ammonia levels (698 µmol/L), which increased to 898 µmol/L despite treatment with lactulose and rifaximin. The diagnosis of urea cycle enzyme deficiency was confirmed by raised levels of urinary orotic acid after allopurinol administration. Hemodialysis was performed, which helped reduce ammonia levels to 38.9 µmol/L. The patient was discharged with citrulline and a protein-restricted diet. Conclusion: This case underscores the importance of considering UCDs in postpartum patients with unexplained coma. The interplay of increased metabolic demands and the disruption of ammonia detoxification due to intrauterine demise or delivery can trigger hyperammonemia. Early diagnosis and prompt treatment, including hemodialysis, are crucial for improving outcomes. Clinical significance: A high index of suspicion for UCDs is essential in postpartum patients presenting with altered sensorium. Frequent serum ammonia level monitoring and timely intervention can prevent severe complications and improve survival rates in these life-threatening conditions.