The current direction of scientific research in recent years has been the study of the immunobiological properties of vitamin D. The purpose of this work was to analyze the results of oral administration of cholecalciferol in order to prevent infection with the SARS-CoV-2 virus in the first wave of the COVID-19 pandemic. The study was performed in the period from October 07 to December 29, 2020, when there were no immunobiological drugs for specific prevention of COVID-19. The total number of respondents was 73 people; all had been ill with coronavirus only once. The etiological diagnosis of the disease included molecular genetic testing of samples of two localizations obtained by the conventional method (nasopharynx, oropharynx). The concentration of antibodies to the virus was determined on average 2 months after the disease using a set of reagents SARS-CoV-2-IgG quantitative-ELISA-Best (JSC Vector-Best, Russia). An approximate assessment of IgM concentration was carried out using a set of SARS-CoV-2-IgM-ELISA-Best from the same manufacturer. Among the study participants were those who used immunobiological drugs for the prevention of infection (riamilovir, umifenovir hydrochloride monohydrate, human recombinant interferon alpha-2b, zinc acetate, vitamin C). In particular, 28 people (38.4%) took cholecalciferol (group No. 1) and 45 people (61.6%) did not use this (group No. 2). Statistical processing of the obtained data was performed using the statistical package STATISTICA v.12.5.192.5 (StatSoft, Inc., USA). We applied the analysis of basic statistics, Linear Discriminant Analysis, Kolmogorov–Smirnov test, Chi-Square test, Wald–Wolfowitz Runs Test, Kruskal– Wallis test. Differences in the incidence of respiratory distress syndrome of the two studied groups were revealed: in patients taking cholecalciferol, the syndrome did not develop at all; in group No. 2, it was registered in 20.0% of cases (Chi-Square = 5.242, p = 0.02). In addition, in patients of group No. 1, the concentration of IgG 2 months after the disease was 3.8 times higher than the values in group No. 2 (Chi-Square = 9.268, p = 0.003). Similar differences were found for the IgM level (Wilks' Lambda: 0.659 approx. F (7.32) = 2.367 p < 0.045). It was known that in both groups there were respondents who used other immuno-active substances for preventive purposes. In the first group there were 18 people (24.7% of all); in the second, there were 13 people (17.8% of all). It was found that those who used other immuno-active substances and did not take vitamin D suffered the disease more easily than everyone else. The respondents who did not use any immunoprophylactic agents were the next in terms of the severity of the infection. The respondents who took cholecalciferol mainly assessed the severity of the infection as average. The study participants who took both vitamin D and used other means of prevention suffered the most from COVID-19. Respondents who took cholecalciferol more often than others reported long-term fatigue, exacerbation of chronic and the appearance of new diseases (hypertension, cardialgia, bronchial asthma, allergies, decreased visual acuity), muscle, joint and vertebral pains that appeared for the first time. The phenomenon of arthralgia and other lesions of large joints in COVID-19 was described by us earlier. Studies by other authors also report frequent complaints of increased fatigue and joint pain. At the same time, the role of vitamin D is considered exclusively from the standpoint of vitamin deficiency in a new coronavirus infection and its potential role in inhibiting hyperinflammatory reactions, as well as accelerating the healing process of affected areas, especially in lung tissue. It was found that vitamin D intake did not affect the incidence of fever, the incidence of pneumonia, the volume of lung tissue damage (based on computed tomography data), the duration of hospitalization and the disease as a whole, and also did not prevent the development of anosmia and dysgeusia. The use of vitamin D as a protective agent to prevent infection with the SARS-CoV-2 virus has had an impact on reducing the frequency/ prevention of cases of respiratory distress syndrome during the disease. Also, those who took vitamin D recorded an increase in the formation of IgG to the SARS-CoV-2 virus 2 months after infection 3.8 times higher than the values recorded in respondents who did not take cholecalciferol. The participants who took cholecalciferol suffered the infection more severely, especially if they used any other protective substances. Also, with the preventive intake of vitamin D after COVID-19, increased fatigue persisted longer, the appearance of new and activation of chronic diseases and muscle, joint and vertebral pains that appeared for the first time were reported more often, which correlates with the data we received earlier.