Infants with respiratory distress syndrome (RDS) may suffer from severe hypoxia, asphyxia. In this study, we aimed to evaluate serum ischemia-modified albumin (IMA) level as a diagnostic marker for hypoxia in preterm infants with RDS. Thirty-seven premature newborns with RDS were allocated as the study group and 42 healthy preterm neonates were selected as the control group. IMA was measured as absorbance unit (ABSU) in human serum with colorimetric assay method which is based on reduction in albumin cobalt binding. IMA levels were significantly higher in neonates with RDS as compared to the control group (P < 0.001). Cut-off value of IMA (ABSU) was 0.72, the sensitivity level was 91.9 %, the specificity was 78.6 %, positive predictive value was 79.1 % and negative predictive value was 91.7 % at RDS. Area under curve values was 0.93 (P < 0.001; 95 % CI, 0.88-0.98) in the receiver operating characteristic curve. We concluded that elevated blood IMA levels might be accepted as a useful marker for hypoxia in newborn with RDS.