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OBJECTIVE: Corona Virus Disease-2019 (COVID-19) has been among the major infectious events of the century. In today's literature where COVID-19 and host factor effects are frequently examined, we aimed to examine another factor: Circadian Clock Protein PERIOD 3 (PER3). There is a significant correlation between PER3 gene polymorphism and circadian rhythm disturbances and immune system dysregulation. METHODS: In our study, we recruited 200 patients diagnosed with COVID-19 in our hospital between April-June 2020, and 100 volunteers without known comorbidities to create a healthy control group. After comparing the initial gene polymorphisms of the patients with healthy controls, three separate clinical subgroups were formed. Gene polymorphism distribution and statistical significance were examined in the formed patient groups. RESULTS: No significant difference was found between the patient group and the healthy controls (P>0.05, for all). When patients were divided into two separate clinical subgroups as exitus/alive according to their last condition during their 28-day follow-up, the 4R/5R genotype was significantly more common in patients with a mortal course (P=0.007). The PER3 4R/5R genotype was found at a significantly higher rate in the group of patients with the need for intensive care (P=0.034). CONCLUSION: The 4R/5R genotype may be associated with the need for intensive care and mortality in COVID-19 patients. These important results will be a guide for future studies.