The article analyzes how long-duration space missions effect on the heart rate variability parameters and invariable blood proteins. The results are discussed taking into correlation between them. Seven Russian cosmonauts took part in the research during their missions to the International Space Station. Samples of dry blood drops were collected as part of the space experiment ''OMICs-SPK'', electrocardiogram samples were collected as part of the space experiment "Cardiovector". It was established a linear relationship between the concentrations of some proteins and spectral analysis parameters of heart rate at all stages of space flight. In the context of the physiological cardiovascular regulation, the linear correlation found between the six invariant proteins and HRV may be evidence of how and to what extent an adaptive regulation system provides flexible control over the periphery when several processes influence each other. The heart rate variability provides high adaptability, which makes it possible to quickly cope with the challenges of an aggressive and changing environment, maintain homeostatic processes and provide valuable information about the body's ability to function effectively in microgravity.