We aimed to investigate the role of procalcitonin in the diagnosis and follow-up of neonatal sepsis, and to compare it with C-reactive protein (CRP) in this context. Between April and October 2002, a total of 67 neonates were randomly recruited into the study and were divided into four groups as: those with highly probable sepsis (group 1), probable sepsis (group 2), possible sepsis (group 3), and no sepsis (group 4; controls). When the initial procalcitonin levels of the groups were compared, the results were statistically significant (p < 0.05) except for the comparison between groups 3 and 4 (p > 0.05). When the initial CRP levels were compared between the groups, the levels measured in groups 1 and 2 were significantly higher than the levels measured in groups 3 and 4 (p < 0.05). In addition, the decreasing levels in procalcitonin were statistically more significant than the decreasing levels in CRP in showing the response to antibiotic treatment (p < 0.01 and p < 0.05, respectively). In conclusion, serum procalcitonin levels seemed to be superior to serum CRP levels in terms of early diagnosis of neonatal sepsis, in detecting the severity of the illness, and in evaluation of the response to antibiotic treatment.