Background: Diabetes insipidus (DI) is a rare cause of hypernatremia in preterm newborns. Common causes of central DI include intra-ventricular hemorrhage, congenital infection and midline defects. Nephrogenic DI (NDI) is less frequent and can be caused by nephrocalcinosis. Case Report: We hereby report 665 gram female infant born at 27 weeks gestation with central DI and treated with desmopressin. The infant presented again with hypernatremia and showed a poor response to desmopressin. The finding of nephrocalcinosis oriented us to a nephrogenic component of DI. Conclusion: Although nephrogenic diabetes insipidus is the less frequent form of DI, preterm newborns present many risk factors for developing nephrocalcinosis (prolonged ventilation, diuretic therapy, dexamethasone, hypercalcemia) and NDI as a result. In a preterm newborn with CDI, a nephrogenic component must be suspected in the set of decreasing response to DDAVP.