question: BACKGROUND AND AIMS: This study aimed to evaluate serum 25-hydroxyvitmain D and zinc levels in coronavirus disease 2019 (COVID-19) patients in comparison to healthy subjects. METHODS: This was a single-center case-control study performed from March 20, 2020, to January 20, 2021, in Tehran, Iran. All patients diagnosed with COVID-19 based on a positive nasopharyngeal swab polymerase chain reaction (PCR) test were included in the case group. Controls were selected from patients referred for routine checkups who had a negative COVID-19 PCR test. Age, sex, marital and educational status, comorbidities, and serum 25-hydroxyvitmain D and zinc levels of patients were recorded. RESULTS: Ninety patients in the case group and 95 subjects in the control group who were sex and age-matched were studied. 25-hydroxyvitmain D levels lower than 20 ng/ml were observed in 58 (64%) cases and 72 (76%) controls (P = 0.09). The median 25-hydroxyvitmain D level in the case group was significantly lower than controls (26 (interquartile range [IQR] = 24) ng/ml vs. 38 (IQR = 22) ng/ml, respectively, P < 0.01). The median zinc level in the case group was 56 (IQR = 23) ng/ml, while it was 110 (IQR = 27) ng/ml among the controls (P < 0.01). There was no significant difference in the level of 25-hydroxyvitmain D and zinc between cases with and without comorbidities (P > 0.05). Susceptibility to SARS-CoV-2 infection could be predicted by serum 25-hydroxyvitmain D levels below 25.2 ng/ml (81% sensitivity; 48% specificity) or zinc levels below 86.3 mmol/ml (93% sensitivity; 92% specificity). CONCLUSIONS: Low serum zinc and 25-hydroxyvitmain D levels appear to be risk factors for COVID-19 affliction; thus, the treatment of individuals with such deficiencies is recommended.