Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstriction peptide present in human plasma. In this study, plasma ET-1 concentrations were determined and compared to renal function changes and other clinical parameters in hypoxic neonates. This study included forty newborns [22 with Hypoxic Ischemic Encephalopathy (HIE), 8 with Respiratory Distress Syndrome (RDS) and 10 healthy newborns as a control group]. Endothelin-1 was significantly elevated in the hypoxic neonates when compared to normal healthy neonates (3.98 ± 1.41 vs. 2.6 ± 0.2 pg/mL, p<0.001). ET-1 was significantly positively correlated to Blood Urea Nitrogen (BUN), serum creatinine and mortality, while it was significantly negatively correlated to serum sodium and calculated GFR. Finally ET-1 was found to be a highly significant predictor of mortality with high sensitivity and moderate specificity. It was concluded that endothelin-1 is a reliable marker for perinatal hypoxia and correlates significantly with renal impairment and subsequent mortality.