Background: C-reactive protein (CRP) is used to assist the diagnosis and monitoring of newborn infection. Little is known about CRP activity after birth in the absence of infection. Objective: The aim of this work was to describe postnatal CRP responses in the first days of life in asymptomatic infants with a negative blood culture. Methods: Data were collected from infants who had a blood culture taken at <72 h of age in a UK maternity hospital. All CRP values and their time from birth were recorded. Infants with signs of infection, positive blood culture, or major congenital anomalies were excluded. Infants were analysed by gestation (greater or less than 37 weeks). Normalised CRP curves were generated by linear interpolation and centile curves were derived. Comparisons of median CRP values between groups were made by Mann-Whitney U test at 24, 36, and 48 h. Results: During the study period a total of 219 babies were screened. After exclusions, 73 infants (58 term, 15 preterm) were analysed. In asymptomatic term neonates the CRP (mg/L) peaked at 9.4 after 34.6 h. In preterm babies the CRP peak was 1.75 at 43 h. The median (IQR) values were higher in the term group at 24 and 36 h: 2.5 (1-10.5) versus 0 (0-2.2; p = 0.02) and 3 (0-8.6) versus 0 (0-2.8; p = 0.031). Conclusions: A CRP rise was demonstrated in term and preterm infants without evidence of infection. This rise was greatest in term infants. CRP values must be interpreted in the context of an infant's clinical condition and not used alone to guide clinical decision making.