Strenuous exercise or overtraining increases the production of reactive oxygen species (ROS), especially in mitochondria. ROS production in excess leads to oxidative stress, cellular dysfunction, and oxidation of molecules such as DNA, polyunsaturated fatty acids, amino acids, and proteins. Previous research has shown that antioxidant supplementation might lead to the downregulation of ROS production. Coenzyme Q10 is an antioxidant believed to be effective in downregulating the effects of oxidative stress and preventing cellular damage. However, most previous studies have used ubiquinone, an oxidised form of Coenzyme Q10. Ubiquinol, a reduced form of Coenzyme Q10, is highly bioavailable, stable and in a form that the body can readily use. This randomised, double-blinded, crossover-controlled trial investigated ubiquinol's antioxidant and anti-inflammatory effects on biochemical and oxidative stress indexes after an intense bout of exercise in trained athletes. Twenty-one male athletes in constant training were randomly taking 200 mg/day of ubiquinol for a month. After a single bout of intense aerobic and endurance exercise, the participants showed a rapid and significant reduction in ubiquinol levels, especially lipoprotein CoQ10 and increased muscle damage markers such as Creatine kinase (CK) and Myoglobin (Mb). Ubiquinol supplementation prevented exercise-induced CoQ10 scarcity and reduced the activity of paraoxonase, an anti-inflammatory and antioxidant enzyme protective against oxidative stress in lipoprotein and circulating cells. Ubiquinol supplementation was associated with a significant decrease in cytosolic ROS in peripheral blood mononuclear cells. Ubiquinol supplementation enhanced plasma and cellular antioxidant levels. Healthcare professionals can use the results of this study to understand the antioxidant effects of ubiquinol supplementation and its buffering effect on plasma CoQ10 balances and exercise-induced CoQ10 depletion. However, further robust studies are required to evaluate the therapeutic potential of ubiquinol supplementation in sports nutrition.