Background: In neonatal sepsis, the purpose of this study is to investigate the possible diagnostic and prognostic utility of receptor interacting protein 3 (RIP3). Methods: This case control study included 70 participants divided into 2 groups, 35 sepsis cases and 35 controls. Plasma level of Receptor Interacting Protein (RIP3) before and after antibiotic treatment was assessed to all subjected participants. Results: There was highly statistical significant difference between the two groups as regards RIP3 levels. Regarding RIP3 (pg/mL), AUC was 0.848, Cutoff value was 16375.5, Sensitivity was 74.3% and Specificity was 97.1%. Regarding highly sensitive C-reactive protein (hs-CRP) (mg/L), AUC was 0.887, Cutoff value was 3.25, Sensitivity was 74.3% and Specificity was 97.1%. Regarding platelets (PLT) (×109/L), AUC was 0.742, Cutoff value was 189.5, Sensitivity was 80.0% and Specificity was 60.0%. Regarding RIP3 + hs-CRP combination, AUC was 0.848, Cutoff value was 16378.75, Sensitivity was 74.3% and Specificity was 97.1%. Regarding RIP3 + PLT combination, AUC was 0.851, Cutoff value was 16557.5, Sensitivity was 74.3% and Specificity was 97.1%. Regarding hs-CRP + PLT combination, AUC was 0.796, Cutoff value was 194.8, Sensitivity was 88.6% and Specificity was 62.9%. Regarding RIP3 + hs-CRP + PLT combination, AUC was 0.851, Cutoff value was 16560.75, Sensitivity was 74.3% and Specificity was 97.1%. Conclusion: The early detection and comprehension of the therapeutic impact of newborn sepsis may be attributed to RIP3. When diagnosing neonatal sepsis, the simultaneous detection of RIP3, CRP, and PLT may be more useful than their separate detection.