The purpose of this study was to determine the test characteristics of C-reactive protein (CRP) in the diagnosis of septic arthritis in children and to compare with erythrocyte sedimentation rate (ESR). The authors reviewed patients with synovial fluid aspiration sent for culture and Gram stain for whom a CRP was drawn within 24 hours of presentation. Descriptive statistics and univariate analyses were performed. Results for CRP were compared with ESR. Thirty-nine of 133 patients had septic arthritis. Sensitivity of CRP ranged from 41% to 90%, specificity from 29% to 85%. Positive predictive values ranged from 34% to 53%, negative predictive values from 78% to 87%. In comparison to ESR, CRP is a better independent predictor of disease. CRP is a better negative predictor than a positive predictor of disease. Indeed, if the CRP is <1.0 mg/dL, the probability that the patient does not have septic arthritis is 87%.