Nowadays, manned cosmonautics is faced with the task of carrying out a long-term space flight beyond the limits of low Earth orbit. Under the conditions of an orbital space flight, a person is exposed to a number of adverse effects on the body, among which microgravity is especially distinguished. Prolonged exposure to microgravity can lead to severe immune impairment. At present, immunological studies of cosmonauts can be conducted only after they return to Earth at the end of a space flight, as a result of which the use of ground-based models that imitate specific space factors seems to be an advanced direction. A well-studied microgravity model is bed rest, during which volunteers are kept in strict rest in bed. Granulocytes, as representatives of innate immunity, are the first among immune cells to respond to an altered state of the body; therefore, researches of the influence of bed rest on the granulocyte phenotypic characteristics can provide important information for the development of prophylaxis measures to the immune disorders’ development when exposed to microgravity. The work used data obtained from six subjects. The impact of bed rest was determined at the end of the model, after 21 days. The following granulocyte clusters of differentiation (CD) were studied by flow cytometry: CD25, CD64, CD23, CD14, CD16, CD36, CD11b, CD18, CD286. Tendencies to a decrease in the percentage of CD64+ subpopulation and an increase in the percentage of CD23+, as well as CD25+ subpopulation of granulocytes after 21 days of bed rest were revealed.