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To evaluate the effects of Caspase-3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 41 individuals (male: 21; female: 20) with SARS-CoV-2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3  2 - ΔΔ C t (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 2 - ΔΔ C t levels and hemoglobin (p = 0.023), between CASP3 2 - ΔΔ C t levels and C-reactive protein (CRP) (p = 0.001), between CASP3 2 - ΔΔ C t levels and ferritin (p = 0.003), between CASP3 2 - ΔΔ C t levels and lactate dehydrogenase (p =  0.001), and between CASP3 2 - ΔΔ C t levels and SpO 2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO 2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS-CoV-2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease., (© 2021 Wiley Periodicals LLC.)