The aim of the study was to determine the association between the long-term physical activity (PA) and the total antioxidant capacity (TAC) of blood serum and their association with coexisting risk factors of cardiometabolic diseases in a group of relatively healthy men. The research was conducted among 422 males age 19.2-89.8 yr, either sedentary or involved in recreational sports activities. Anthropometric measurements, lipid profile, and measurement of glucose and uric acid levels were performed in every man. Current PA, historical PA, and aerobic fitness (physical working capacity) were assessed. TAC was determined with two spectrophotometric methods: the ferric reducing ability of serum (TAC-FRAS) and 2,2-diphenyl-1-picryl-hydrazyl (TAC-DPPH) tests. TAC was not related to the age of the subjects. Higher current and historical PA were associated with a more favorable cardiometabolic risk profile but not TAC. In fact, current PA level was connected with lower values of TAC-FRAS. Values of both TAC-FRAS and TAC-DPPH decreased with an increase of aerobic capacity. Individuals with coexisting anthropometric and biochemical risk factors of cardiovascular diseases and with elevated values of arterial pressure had higher TAC. Values of both TAC-FRAS (r = 0.66) and TAC-DPPH (r = 0.39) were strongly positively correlated with uric acid level. Overweight, obesity, higher blood pressure, unfavorable blood lipid profile, and especially higher uric acid levels are connected with greater TAC of blood serum across an adult man's life. High PA and fitness are associated with a more favorable overall risk profile of cardiovascular and metabolic diseases but are related to lower TAC.