The integrated response of the human proteome to re-entry g-loads following long-term space missions was studied in 13 male cosmonauts at the age of 44 ± 6 years. Examination at the landing site discovered local petechial hemorrhages into soft tissues of the back and lower legs. The paper presents a new approach to evaluation of petechia and soft tissue hemorrhages in cosmonauts on return to Earth. Proteomic analysis was performed with the use of LC-MS. Bioinformation analysis was made using Perseus, PubMed, Uniprot and ANDSystem software. Nine out of 19 significantly different (p < 0.05) proteins were related to vascular injuries directly. We described proteins with a primarily protecting effect against endothelial cells apoptosis and augmentation of vascular permeability, proteins that are responsible for blood rheology and proteins antagonistic to the main triggers of ischeamia-reperfusion injuries of the lungs, liver and other parenchymal organs.