Abstract: Time-dependent changes in body composition and the levels of hormones involved in regulating energy metabolism and eating behavior were studied in ten healthy volunteers who were exposed to dry immersion (DI) for 21 days without the use of countermeasures to prevent the negative effects of the experimental conditions. Bioimpedance analysis (BIA) was used to assess the body composition in the test subjects. The proportion of lean mass decreased, while the fat component increased in the subjects under the influence of factors of 21-day DI. Cluster analysis isolated two equal homogeneous groups of subjects with a reduced group variability of the parameters of body composition and systemic regulation of energy metabolism. A significant decrease (p < 0.05) in relative skeletal muscle mass (SMM%) was observed after 21-day DI in the group with a higher relative body fat mass (FM), a lower relative fat-free mass (FFM), and a higher basal metabolic rate. SMM was stable, while SMM% increased (p < 0.05) after 21-day DI in the group with a lower relative FM, a higher FFM, and a lower basal metabolic rate. A significant increase in blood insulin was observed during DI in this group. Leptin and triglyceride concentrations differed between the groups in different periods of the experiment. © 2021, Pleiades Publishing, Inc.