Fever after cardiac surgery in children may be due to bacterial infection or noninfectious origin like systemic inflammatory response syndrome (SIRS) secondary to bypass procedure. A marker to distinguish bacterial from nonbacterial fever in these conditions is clinically important. The purpose of our study was to evaluate, in the early postcardiac surgery period, whether serial measurement of C-reactive protein (CRP) and its change over time (CRP velocity) can assist in detecting bacterial infection. A series of consecutive children who underwent cardiac surgery with bypass were tested for serum levels of CRP at several points up to 5 days postoperatively and during febrile episodes (>38.0°C). Findings were compared among febrile patients with proven bacterial infection (FWI group; sepsis, pneumonia, urinary tract infection, deep wound infection), febrile patients without bacterial infection (FNI group), and patients without fever (NF group). In all, 121 children were enrolled in the study, 31 in the FWI group, 42 in the FNI group, and 48 patients in the NF group. Ages ranged from 4 days to 17.8 years (median 19.0, mean 46 ± 56 months). There was no significant difference among the groups in mean CRP level before surgery, 1 hour, and 18 hours after. A highly significant interaction was found in the change in CRP over time by FWI group compared with FNI group (P < .001). Mean CRP velocity ([fCRP - 18hCRP]/[fever time (days) - 0.75 day]) was significantly higher in the infectious group (4.0 ± 4.2 mg/dL per d) than in the fever-only group (0.60 ± 1.6 mg/dL per d; P < .001). A CRP velocity of 4 mg/dL per d had a positive predictive value (PPV) of 85.7% for bacterial infection with 95.2% specificity. Serial measurements of CRP/CRP velocity after cardiac surgery in children may assist clinicians in differentiating postoperative fever due to bacterial infection from fever due to noninfectious origin.