Neonatal central diabetes insipidus (DI) is an extremely rare disorder that can cause severe morbidity and mortality. We have reported a very low birth weight infant with idiopathic central DI presenting in the first month of life who was successfully treated with sublingual desmopressin therapy. In this report, we emphasize that central DI should be kept in mind in an infant with unexplained hypernatremia and polyuria. Timely diagnosis and treatment with lyophilized desmopressin may prevent severe morbidity and mortality.