Background: Collodion baby is a rare condition (i.e., 1: 300000 birth), which is referred to a neonate covered with a tight and shiny membrane desquamating within two weeks. This condition takes place as a result of the epidermal cornification disorder. Given the impairment of the skin barrier function, these neonates are at the risk of several complications, including hypernatremic dehydration, hypothermia, skin infections, fissures, conjunctivitis, sepsis, dehydration, and constrictive bands of the extremities resulting in vascular compromise and edema. This condition has a high mortality rate; accordingly, the majority of the collodion babies die within the first few weeks of birth due to the secondary complications depending on the type of mutations. Although the collodion membrane is a transient condition, it can lead to a number of complications in 45% of the newborns and result in 11% mortality rate in the first few weeks of the neonatal life. However, in the recent years, the mortality rates have been declined owing to the introduction of systemic retinoids to the clinical practice and the advanced care methods, which are used in the intensive care units. Harlequin ichthyosis has been associated with the mutation in the ABCA12 gene; therefore, genetic counseling and mutation screening of this gene should be considered.Case report: Herein, we reported a case of a collodion baby with favorable evolution, who developed HYPERNATREMIA and suffered from some complications having aroused from the condition.Conclusion: Infection prevention and supportive care of collodion babies mainly with incubator, serum therapy, and feeding support can be effective in preventing complications.