Neonatal disease severity scoring systems are needed to make standardized comparison between performances of different units and to give prognostic information to parents of individual babies admitted. Existing scoring systems are unsuitable for resource-limited settings which lack investigations like pH, pO2/FiO2 ratio, and base excess. This study was planned to evaluate Modified Sick Neonatal Score (MSNS), a novel neonatal disease severity score designed for resource-constrained settings. It was a facility-based cross-sectional analytical study, conducted in the “Special Newborn Care Unit“ (SNCU) of government district hospital, attached to Kasturba Medical College, Mangalore, India from November 2016 to October 2017. A convenience sample of 585 neonates was included. Disease severity was assessed immediately at admission using MSNS. MSNS had 8 parameters with 0, 1, and 2 scores for each. 41% of study population was preterm (), and 84.1% had birth weight less than 2500 grams (). The mean (SD) of the total MSNS scores for neonates who expired and discharged was, respectively, 8.22 (2.96) and 13.4 (2.14), a difference being statistically significant at . Expired newborns had statistically significant frequency of lower scores across each of the parameters. An optimum cutoff score of ≤10 with 80% sensitivity and 88.8% specificity in predicting mortality was obtained when the ROC curve was generated with the MSNS score as the test variable. Area under the curve was 0.913 (95% CI: 0.879–0.946). In conclusion, MSNS is a practicable disease severity score in resource-restricted settings like district SNCUs. It is for application in both term and preterm neonates. Total score ≤10 has a good sensitivity and specificity in predicting mortality of admitted neonates when used early during the course of hospitalization. MSNS could be used as a tool to compare performance of SNCUs and also enable early referral of individual cases to units with better facilities.