Purpose. The aim of this study was to evaluate the sensitivity of pleural C-reactive protein (CRP) biomarker levels in identifying parapneumonic effusions. Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, post-lung transplantation, and parapneumonic effusion. Results. The pleural CRP levels significantly differentiated the four groups (p < 0.001) with the following means: parapneumonic effusion, 5.38 ± 4.85 mg/dL; lung transplant, 2.77 ± 2.66 mg/dL; malignancy, 1.19 ± 1.51 mg/dL; and heart failure, 0.57 ± 0.81 mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37-1.89). Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology.