OBJECTIVE To determine the potential predictive power of C-reactive protein (CRP) as a marker of serious bacterial infection (SBI) in hospitalized febrile infants aged < or =3 months. METHODS Data on blood CRP levels were collected prospectively on admission for all infants aged < or =3 months who were hospitalized for fever from 2005 to 2008. The patients were divided into two groups by the presence or absence of findings of SBI. RESULTS A total of 892 infants met the inclusion criteria, of whom 102 had a SBI. Mean CRP level was significantly higher in the infants who had a bacterial infection than in those who did not (5.3 +/- 6.3 mg/dL vs. 1.3 +/- 2.2 mg/dL, p < 0.001). The area under the ROC curve (AUC) was 0.74 (95% CI: 0.67-0.80) for CRP compared to 0.70 (95% CI: 0.64-0.76) for white blood cell (WBC) count. When analyses were limited to predicting bacteremia or meningitis only, the AUCs for CRP and WBC were 0.81 (95% CI: 0.66-0.96) and 0.63 (95% CI: 0.42-0.83), respectively. CONCLUSIONS C-reactive protein is a valuable laboratory test in the assessment of febrile infants aged < or =3 months old and may serve as a better diagnostic marker of SBI than total WBC count.