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Significant advances have been achieved in immunotherapy for the treatment of lung cancer. It is known that tumor cells and cells in the tumor microenvironment express high amounts of programmed cell death ligand 1 (PD-L1). These PD-L1s interact with programmed cell death protein 1 (PD-1), causing immunosuppression. The aim of our study is to examine the correlation between the serum sPD-1 and sPD-L1 levels and clinicopathological characteristics in patients with nonsmall cell lung cancer. We also compared our results with the healthy population (control group).Thirthy-seven nonsmall cell lung cancer (NSCLC) patients who were operated in our clinic were included in our study. The control group included fifteen healthy patients. The sPD-1 and sPD-L1 levels were measured in serum samples by using the ELISA method.The preoperative sPD-1 and sPD-L1 levels were significantly higher in the study group compared to the control group (44.12 ± 22.25 pg/mL vs. 18.54 ± 6.56 pg/mL; p = 0.001 and 26.15 ± 18.03 pg/mL vs. 10.29 ± 3.08 pg/mL; p = 0.001, respectively). There was a statistically significant decline in serum sPD-1 and sPD-L1 levels at the preoperative and postoperative 1st, 7th, and 30th days following surgical resection (44.12 ± 22.25 pg/mL, 37.86 ± 18.02 pg/mL, 36.33 ± 18.36 pg/mL, 34.14 ± 13.71 pg/mL; p = 0.007 and 26.15 ± 18.03 pg/mL, 20.60 ± 15.50 pg/mL, 18.31 ± 14.04 pg/mL, 13.64 ± 10.60 pg/mL; p = 0.001, respectively).There was a positive correlation between the preoperative and postoperative 30th day serum sPD-1 levels and the tumor size (p = 0.031, r = 0.352; p = 0.024, r = 0.371; respectively). We also found a positive correlation between the preoperative and postoperative 30th day serum sPD-L1 levels and pleural invasion (p = 0.001, p = 0.001; respectively), and the N category (p = 0.015, p = 0.013; respectively).We think that sPD-1 and sPD-L1 levels may be used as a potential biomarker for lung cancer screening, prediction of the stage, and besides to detect recurrences and/or metastases following resection in NSCLC following validation with multicenter and larger-scale prospective trials.