The concept of illness severity scoring has been around for long and is currently being utilized in many neonatal intensive care unit (NICU). Scoring systems that help to quantify mortality risks on the basis of clinical conditions not only help in estimating prognosis, but also help clinicians in making decisions particularly in situations presenting with dilemmas. This study aims to determine SNAPPE-II (Score for Neonatal Acute Physiology-Perinatal Extension) score as a predictor of neonatal mortality in NICU at a tertiary care hospital in Pakistan. MethodologyIt was a longitudinal cohort study. The study was conducted at a neonatal intensive care unit (NICU) of Aga Khan University Hospital (AKUH) Karachi, Pakistan. All neonates were included who were born in AKUH and who needed respiratory support in NICU. ResultsA total of 333 newborns were enrolled for this study. Out of those 30 (9.1%) neonates expired while 298 (90.9%) survived. Area Under the Receiver operative curve was calculated to obtain the SNAPPE-II score's diagnostic discrimination ability. Area under the curve (AUC) was 80.2±4.6% which corresponds to a moderate diagnostic accuracy for the prediction of neonatal mortality. The 95% CI for this was between 71.1-89.2%. SNAPPE-II category III (>40) was found to be the strongest predictor of mortality, with a sensitivity of 40% and a specificity of 98.7%. ConclusionThe SNAPPE-II scoring system, we conclude, might be a valuable technique for predicting newborn death in resource-constrained NICUs.