© 2021 John Wiley & Sons LtdObjective: In the present study, we aimed to differentiate between transudative and exudative pleural effusions using thiol sulphide homoeostasis, an oxidative stress marker. Design: This was a prospective study. Setting: Emergency Department of Ankara City Hospital, between 1 January 2020 and 15 May 2020. Subjects: Patients who were diagnosed with pleural effusion and underwent thoracentesis to make a differentiation between transudative and exudative pleural effusions. The patients were divided into two groups as those who have transudative pleural effusion and those who have exudative pleural effusion. These two groups were assessed with respect to demographic features and oxidative stress parameters. Main Outcome Measures: Oxidative stress parameters (The native thiol (NT), total thiol (TT), and disulphide (D) levels and their ratios to one another were calculated (index 1: D/NT, index 2:D/TT, index 3: NT/TT). Results: This study enrolled a total of 50 patients with pleural effusion. Twenty patients (40%) were men, and 30 patients (60%) were women. In the transudative pleural effusion group, 14 patients (56%) had decompensated heart failure, 9 patients (36%) had hepatic cirrhosis, and 2 patients (8%) had hypoalbuminemia. In the exudative pleural effusion group, 17 patients (68%) had malignancy, 7 patients (28%) had parapneumonic effusion, and 1 patient (4%) had pulmonary embolism. TT (P <.001) and NT (P =.001) values were significantly lower in the transudative pleural effusion group compared with the exudative pleural effusion group whereas there was no significant difference between the two groups with respect to D (P =.489), index 1 (P =.07), index 2 (P =.064), and index 3 (P =.063) values. Conclusion: We believe that a differentiation can be made between transudative and exudative pleural fluids by using thiol sulphide homoeostasis, an oxidative stress marker.