Background: Sarcoidosis is a chronic inflammatory disease that primarily affects the lungs and lymph nodes. The formation of noncaseating granulomas is one of the characteristics of this multisystem disorder of unknown etiology. The purpose of this study was to assess the value of soluble interleukin-2 receptor (SIL2R) and serum angiotensin-converting enzyme (SACE) levels in the diagnosis of sarcoidosis. Materials and methods: This case–control study recruited 37 patients with newly diagnosed pulmonary sarcoidosis and 31 healthy controls. All subjects had blood samples taken in order to determine their levels of SACE and SIL2R. Chest X-rays, spirometry with diffusion capacity for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) scans were performed on the sarcoidosis patients. Results: The mean values of serological parameters SACE and SIL2R were (79.49 ± 35.78 U/mL and 672.84 ± 408.86 pg/mL) in cases and (35.81 ± 9.45 U/mL and 300.03 ± 529.77 pg/mL) in controls, respectively. Differences were statistically significant for all these parameters, with a significantly higher mean in sarcoidosis patients. Sensitivity and specificity for SACE and SIL2R were 94.59, 93.55, 91.89, and 87.10%, respectively. Conclusion: This study suggests that SACE and SIL2R are useful markers for the diagnosis and monitoring of sarcoidosis. In sarcoidosis patients, SIL2R levels may also serve as a predictor of the disease progression and pulmonary function. © 2025 Elsevier B.V., All rights reserved.