Respiratory distress is associated with lung maturation and vitamin D which is explained by the mechanism of production and secretion of phospholipids (surfactants) on the surface of type II alveolar cells (ATII). To determine the differences between in vitamin D levels in premature neonates with respiratory distress in premature neonates and without respiratory distress. Analytical analyses with a case-control study in premature neonates who experienced respiratory distress at the H. Adam Malik Medan General Hospital from September 2021 to March 2022. To assess the difference among variables with t-independent test, Mann-Whitney test, and Kruskal Wallis test. A total of 25 patients with respiratory distress samples and 25 controls were analyzed. Differences between the classification of vitamin D levels in children with respiratory distress and without respiratory distress had a significant (p=0.014) with vitamin D level with respiratory distress of 14.72. The difference between Downe Score and APGAR Score in children with respiratory distress and without respiratory distress also had significance (p=0.001) with a mean of Downe Score of 4.68 and APGAR Score of 5.96 for the first 7.16 for the fifth, and 7.6 for the tenth minutes. The differences between Downe Score and vitamin D levels in the group of infants with respiratory distress did not have a significant (p=0.742). There are significant differences among the classification of vitamin D levels, Downe Score and APGAR Score in neonates with respiratory distress and without respiratory distress. However, there was no significant differences between Downe Score and vitamin D levels.