OBJECTIVE The aim of this prospective, observational study was to establish the prognostic values of plasma antithrombin III (ATIII) and protein C (PC) functional levels, determined in 150 neonates with suspected late-onset sepsis. METHODS Both the ATIII and PC concentrations were significantly lower in neonates with sepsis, either confirmed or not confirmed by blood culture, than data obtained in infants with excluded disease. The lowest values of plasma ATIII and PC were observed in neonates who had died in the course of sepsis. The differences between survivors and non-survivors were statistically significant (respectively, for ATIII P=0.003 and for PC P=0.00002). A highly statistically significant correlation (P=0.0016) between plasma PC functional level and risk of death was found in patients with sepsis. However, plasma ATIII concentration, evaluated in the same group of patients, did not correlate with the occurrence of death. CONCLUSIONS We concluded that the measurement of plasma ATIII and, especially, PC levels may facilitate the recognition of sepsis and, with respect to PC, may have a prognostic value. Plasma PC functional concentration below 10% might be the indication for supplementation of PC concentrate.