Neonatal sepsis is one of the leading causes of neonatal morbidity and mortality in the newborn period. The purpose of this study was to compare a rapid bed-side test against central laboratory analysis for CRP in newborn infants with suspicion of sepsis. We included 23 newborn infants with suspected or proven sepsis (group 1). Age and gender matched 40 infants without sepsis were assigned as controls (group 2). A total of 116 blood samples (58 samples from each group) were drawn from the peripheral vein for C-reactive protein (CRP) measurements. For the NycoCard CRP tests, 5 microL of whole blood and the same amount of serum was used to determine the CRP value (wCRP-N and sCRP-N). As the reference CRP test, serum concentrations of CRP (CRP-Lab) were simultaneously measured by immunonephelometric method requiring 1 mL of serum sample. CRP values > or = 10 mg/L were considered positive for all three tests. It was found that the median values of wCRP-N (18.9 mg/L), sCRP-N (25 mg/L), and CRP-Lab (22.2 mg/L) of group 1 were higher than group 2 (wCRP-N: 1.1 mg/L, sCRP-N: 5 mg/L, and CRP-Lab: 2.9 mg/L) (p < 0.001). Nycocard-CRP were positively correlated with CRP-Lab. With considering CRP-Lab positive at > 10 mg/L, both CRP-NycoCard tests have high sensitivity and specificity, although sCRP-N has slightly higher predictive values. Passing-Bablok regression and Bland-Altman analysis showed that NycoCard tests have no statistically significant systematic proportional bias. Nycocard-CRP tests have high predictive values, require a very small amount of blood, and results can be obtained quickly. Determinations of CRP concentrations by NycoCard-CRP test seems to be helpful in distinguishing septic and aseptic newborns.