Abstract Background β2-microglobulin (β2-m) is a biomarker used in serum for different types of pathologies. It has been described that lymphocyte activation processes us tuberculosis infections, AIDS virus or cytomegalovirus infections, can produce an increase in the concentration of this marker. As a tumor marker is useful in lymphomas diagnosis. In the bibliography has reported that processes involving renal failure lead to a significant increase in its concentration. In patients with renal failure and treated with hemodialysis, have been described medians twenty times the upper reference limit. The objective is to assess whether the concentration of (β2-m) in pleural fluid is affected by the same factors as in serum. Methods We analyzed 303 pleural effusions (PE) samples from undiagnosed patients with pleural effusion. β2-microglobulin levels were prospectively measured by electrochemiluminescence (ECLIA) assays (Cobas c702, Roche Diagnostics®). Glomerular filtration rate (GFR) was calculated by CKD-EPI equation. The diagnostic performance of β2-microglobulin was evaluated by receiver operating characteristic (ROC) curve analysis. Statistical analyses were performed using SPSS software. Results Pleural fluid of 303 patients (104 female, 204 male) were collected. The median age was 72 ± 10,6 years. For all samples β2-m median concentration was 5,85 mg/L (IQR:3.4 -6.45).When we compared all results according to kidney failure values; GFR >60mL/min β2-m median concentration was 4,12mg/L and if GFR <60 mL/min, β2-m was 8,62g/L significant difference have found (p<0,001). Comparing results between malignant pleural effusions (MPE) (n=96) and benign pleural effusions (BPE) (n=207), MPE median concentration was 5.38 mg/L and 6.07mg/L significant difference (p<0,001). Benign pathologies associated with pleural effusions, tuberculosis samples had the highest concentration of β2-m. Tuberculosis samples (n=6) had a normal distribution, obtaining a value [mean (SD)] of 7.28 mg/mL (2,13) mg/mL. For tuberculosis samples and patients without renal failure (n=5) (GFR>60 mL/min), the area under the ROC curve was 0.98 (95% CI: 0.88-0.98) (p<0.005). For β2-m cut-off point was 5.150 mg/L, a sensitivity of 100%, specificity of 16%, positive predictive value (PPV) of 14% and negative predictive value (NPV) of 100% were obtained. Patients with lymphomas present the highest concentration in the group of malignant pleural effusions, but further investigations could not be performed due to the small sample size. Conclusions Based on the results obtained from our present study, it can be concluded that β2-microglobulin marker in pleural effusions has significant association with glomerular filtration rate, as well as occurs in serum. Higher concentrations were found in patients with GFR>60 mL/min and tuberculosis. Using 5,15 mg/L cut-off point, 100% of NPV was obtained.