INTRODUCTION: In the developing countries, neonatal sepsis is the most common complication in neonatal period. It is as a systemic inflammatory response because of infection. Laboratory indicators, do not have satisfactory sensitivity. Thus, early identification of sepsis is still needed. Because PTX3 may be a faster acute-phase protein that is not liver-dependent, it is probable that it is superior to traditional biomarkers for mirroring rapid inflammatory courses. METHODS: A prospective case control study design was used to determine the sensitivity of pentraxin 3 in the diagnosis of neonatal sepsis to allow early diagnostic tool. This study was carried out on neonatal ICU unit in Suez Canal University Hospital and the studied population were divided into two groups, including patients diagnosed with neonatal sepsis, based on clinical, laboratory and positive blood culture results, and control group RESULTS: The study found that there was statistically significant differences between both groups in serum CRP values in diseased and control group (Mean = 49.3±37.4 mg/L, 26.8±17.2 mg/L, p < 0.05), and pentraxin values in diseased and control group (Mean = 5.2±3.7 mg/L, 2.3±0.78 mg/L, p < 0.0001). In addition, there were statistically significant correlations between pentraxin and serum CRP concentrations (p < 0.05) in diseased group. ROC curve showed that serum CRP demonstrated good diagnostic accuracy in predicting neonatal sepsis AUC = 0.875 with sensitivity of 100% and specificity of 92.3%. CONCLUSION: Serum PTX3 may be a promising acute-phase protein for interpretation of affected newborns with symptoms and signs of sepsis.