Abstract. Background: Neonatal sepsis is frequently associated with multiple hematologic abnormalities, including depletion of protein C. The status of protein C is not known in infants who clinically present with a sepsis-like picture without a culture-proven sepsis. The objectives of this study were to determine whether sepsis-like illness is associated with a reduction in protein C. Methods: In this case-control, cross-sectional study, 49 full-term neonates admitted to the neonatal intensive care unit (NICU) with the clinical manifestation of sepsis that was not proven by cultures. Fifty healthy full-term newborns were also randomly selected as a control group. Protein C concentrations were compared between both groups. Results: There was no difference between the case and control groups regarding sex and gestational age. Protein C concentration did not differ between groups (p > 0.05); mean protein C concentration was 29.4% of the normal adult level in cases with clinical sepsis and 32% in the control group. Conclusion: Protein C deficiency was not related to clinical manifestations in sepsis-like illness. Further studies examining other predictors of sepsis-like illness are recommended.