Background Pleural effusion is considered an interesting clinical problem that is commonly faced by physicians and is caused by several diseases. The ability of computed tomography (CT) to differentiate transudate effusion from exudate effusion is still under research. Objective The aim of this study was to assess the accuracy of the CT in diagnosing the nature of the pleural effusion. Patients and methods In this prospective cross-sectional analytic study, laboratory biochemistry markers were used to classify pleural effusion into exudate or transudate based on Light’s criteria. Chest CT without contrast had been done for all patients, and CTs were diagnosed by the radiologist. Measurement of the pleural fluid density was done and shown using the CT attenuation values [Hounsfield unit (HU)]. Results Of 79 patients with pleural effusion, 60 patients had exudate effusion and 19 patients had transudate. The mean attenuation values were significantly higher in exudate effusion (20.11±7.11 HU) versus transudate effusion (13.8 ±4.11 HU), with P value of 0.03. Receiver operating characteristic curve analysis showed that the cutoff for exudate effusion was optimal at greater than or equal to 15.33 versus less than 15.33 HU for transudate (area under the curve=0.57; 95% confidence interval: 0.45–0.68). This point had 85.71% sensitivity and 46.55% specificity. Conclusion We reasoned the CT attenuation values of the pleural fluid may replace the laboratory tests in characterizing the pleural effusion, either exudate or transudate. However, there was an overlapping HU values in most effusions. So correlation of the CT results with the clinical findings is essential, and further CT studies are highly recommended to confirm and validate these findings.