Background: Sarcoidosis and tuberculosis (TB) are two granulomatous inflammatory diseases with several common symptoms. The aim of the present study was to compare the serum levels of biomarkers including interleukin-4 (IL-4) and IL-13, calcium (Ca), hemoglobin, sedimentation rate, and lymphocyte-to-neutrophil ratio between patients with pulmonary TB, patients with sarcoidosis, and control group. Materials and methods: This case-control study was performed on patients referred to the Masih Daneshvari Hospital, Tehran, from April 2017 to 2018. In this study, 24 newly diagnosed patients with active pulmonary TB, 34 patients with pulmonary sarcoidosis, and 30 healthy individuals as the control group were enrolled. Demographic data, erythrocyte sedimentation rate (ESR), the ratio of neutrophil-to-lymphocyte (NLR), serum Ca level, hemoglobin (Hb), and IL-4 and IL-13 were compared between the study groups. Receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity were also calculated using SPSS 16.0 software. Results: The mean age was 47.71 ± 10.88 and 55.25 ± 21.58 years in the sarcoidosis and TB. The mean ESR in sarcoidosis patients was 21.45 ± 13.37 mm/h and 41.4 ± 17 mm/h in the TB group. The percentage of peripheral blood lymphocytes in sarcoidosis and TB patients was 28.02 ± 12.20 and 21.41 ± 12.49, respectively, which was significantly higher among patients with sarcoidosis. NLR was also 2.4 ± 1.6 and 4.4 ± 2.9 in sarcoidosis and TB patients, respectively, which showed a significant difference among the groups. Regarding the evaluation of the level of IL-4 and IL-13 in patients, it is worth noting that IL-4 in patients with sarcoidosis was 90 pg/ml compared to 20 pg/ml for TB patients (P < 0.001). There was no significant difference in the levels of IL-13 in the TB and control groups, which varied between 20 and 80 pg/ml (P = 0.35). However, its value was significantly higher in patients with sarcoidosis (P = 0.01) than in the healthy control group and TB (P = 0.01). The ROC curves showed that the diagnostic cutoff of ESR level, Ca, NLR, and Hb could be valuable due to the area under the curves. The cutpoint of 34 mm/h for ESR had a sensitivity of 86% as well as 80% specificity to distinguish TB from the sarcoidosis. Conclusion: Serum levels of the biomarkers indicated a stronger immunological background in sarcoidosis using NLR, Ca, ESR, and Hb.Keywords: Biomarkers; cytokines; interleukin-13; interleukin-4; sarcoidosis; serum; tuberculosis.