Background: Neonatal sepsis is a global mortality risk, necessitating early identification and use of reliable biomarkers, despite ongoing controversy surrounding their use. 
Objectives: The study aimed to evaluate the values of salivary C-reactive protein (CRP) and serum amyloid A (SAA) for the diagnosis of neonatal sepsis. 
Patients and methods: The study involved 80 neonates with late-onset sepsis (LOS) and 40 healthy controls from June 2022 to October 2023. They underwent a detailed perinatal history, physical examination, complete blood count (CBC), blood culture, salivary CRP, SAA, and comprehensive metabolic panel (CMP) included an electrolyte panel, renal and liver function tests, glucose and calcium. We evaluated salivary CRP and SAA before initiating antibiotic therapy. A positive blood culture confirmed the diagnosis of sepsis. We determined the biomarker diagnostic values using receiver operating characteristic curve (ROC curve) analysis and assessed their sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and diagnostic accuracy. 
Results: Significant differences between cases and controls regarding salivary CRP, serum CRP, and SAA levels (p value <0.001) were present. Cases had higher mean salivary CRP (1.6) and SAA (26.4) levels than controls (0.16) and (3.1) respectively. Additionally, cases had a significantly higher mean serum CRP level (53.4) compared to controls (0.9). A moderately positive correlation was found between salivary CRP, serum CRP, and SAA (r = 0.70), with a significant p value <0.001. 
Conclusion: The study suggests salivary CRP can be a valuable noninvasive biomarker for late-onset neonatal sepsis diagnosis, with comparable results to SAA and serum CRP.