When performing maximum loads, an important criterion for assessing prospects is the achievement of the best result with the least metabolic changes in the body of athletes, which indicates the possibility of further increasing physical performance. The study of the mechanisms of energy supply and the reaction of body systems when testing performance under special conditions is one of the important conditions for the development of additional biochemical criteria for assessing the prospects of athletes. Purpose: To study genetic and physiological predictors of bioenergetic adaptation of skeletal muscles in athletes of cyclic sports. Methods: 76 athletes of cyclic sports (speed skating, running disciplines in track-and-field) of European origin who lived in the Southern Urals region took part in the study. The average age of the study participants was 22.1 ± 2.5 y.o. Experience in sports was at least 5 years. We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. The study of bio-energetic indicators of athletes' physical performance was carried out using the bicycle ergometry method (test with maximum load). Biochemical studies were carried out using a Lactate Scout Plus lactometer. Results: Significant differences were found in the ΔLa (%) indicator: in athletes with a dominant homozygous genotype R/R, lactate clearance during a 10-minute rest after performing a bicycle ergometer load is statistically significantly higher than in athletes with a recessive homozygous genotype X/X (20.14±12.74%, versus 11.11±3.12%; p<0.05). The major allele C (R) was associated with moderate and high lactate clearance (OR = 2.25 [95% CI: 0.99 – 5.11] and OR = 2.24 [95% CI: 0.91 – 5.51], respectively). At the same time, a statistically significant association was identified between the minor allele T(X) and the homozygous genotype TT (XX) with low lactate clearance (OR = 12.14 [95% CI: 1.30 – 13.55]). High values of lactate clearance indicate the utilization of lactate from peripheral blood and more efficient recovery processes in carriers of the major allele C (R). Conclusions: lactate clearance during a 10-minute rest period after a bicycle ergometer test with maximum load and DNA profiling of the ACTN3 gene rs1815739 can be recommended as significant physiological and genetic predictors of bioenergetic adaptation of skeletal muscles in cyclical sports athletes of Caucasian origin in the Southern Urals.