Concentrations of the products of peroxide oxidation of lipids (POL), indices of the system of antioxidant defence (SAD), and the activity of 13 diagnostically significant organic/tissue specific enzymes (DSE) were determined in blood serum of cosmonauts who had participated in short (5-9 days, n = 8), long (125-179 days, N = 15), and superlong (241-366 days, n = 5) missions. To feature an interrelation of the indices under study, the canonical correlation analysis of a set of POL and SAP parameters and DSE activity was performed. Compared with pre-flight values, changes in the POL and SAP parameters were significant in serum only after the long-duration missions. Signs of POL activation were noted following the superlong missions. After the long-duration missions increased was the activity (mainly, within the norm) of DSEs, specific for the organs and tissues functioning of which is stressed in the period of post-flight readaptation (skeletal muscles, myocardium, liver). After the superlong missions, the DSE activity either remained essentially unchanged or decreased. In all the tested groups, highly reliable correlations between POL, SAP, and the DSE activity, traditionally applied in clinical diagnostics, were observed. These advocate for the use of POL and SAP indices in medical diagnostics and prognosis of cosmonauts' health.