Salivary markers could serve as potential noninvasive markers in the diagnosis of neonatal infections. We aimed to investigate the diagnostic role of salivary and serum interleukin 10 (IL-10), C-reactive protein (CRP), mean platelet volume (MPV), and CRP/MPV ratio in the diagnosis of late-onset neonatal sepsis in full-term neonates. Seventy full-term neonates were enrolled in this prospective case-control study, 35 with late-onset neonatal sepsis, and 35 controls. Salivary IL-10, serum IL-10, and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Complete blood (CBC) count was measured by an automated blood cell counter. The salivary IL-10, serum IL-10, CRP, MPV, and CRP/MPV ratio levels were much higher in neonates with late-onset sepsis than in control ( 220 ± 150 vs. 18 ± 9   pg / ml , P < 0.001 ), ( 316 ± 198 vs. 23.7 ± 14   pg / ml , P < 0.001 ), ( 78.2 ± 34 vs. 3.3 ± 1.7   mg / L , P < 0.001 ), ( 11.2 ± 0.9 vs. 8.6 ± 0.4   fL ), and ( 7.08 ± 3.3 vs. 0.4 ± 0.2 , P < 0.001 ), respectively. At the cutoff point of >31 pg/ml, salivary IL-10 showed 97.1% sensitivity and 94.3% specificity. Serum IL-10 at a cutoff value of ≥33.6 pg/ml had a sensitivity of 97.1% and specificity of 80%. MPV showed a sensitivity of 100% and specificity of 94.4% at a cutoff   value ≥ 9.2   fL . CRP/MPV ratio showed a sensitivity of 100% and specificity of 97.1% at a cutoff   value > 0.9 . Salivary and serum IL-10 showed a positive correlation with CRP and CRP/MPV ratio in septic neonates. The current study shows for the first time that both salivary IL-10 and CRP/MPV showed statistically significant differences between neonates with late-onset sepsis and controls. Accordingly, salivary IL-10 could serve as a potential noninvasive biomarker for the diagnosis of late-onset sepsis in full-term neonates.