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The aim of this study was to evaluate somatic, hormonal and immunological changes during the macrocycle of cyclists (9 well-trained men, age 25.6 ± 5.2 years and body weight 72.4 ± 7.35 kg). During the training macrocycle, four exercise control tests were carried out, and biochemical markers were measured in the laboratory. Seasonal training changes did not significantly disturb resting somatic and functional parameters, physical capacity (VO2max), body weight, the number of leukocytes and selected hormones. The secretory system of the organism did not respond significantly to the exercise stress in the training process, even with the increasing share of anaerobic processes in the subsequent periods of the macrocycle. Irisin and other parameters globally did not correlate with training volume. Irisin showed a significant correlation only with cortisol in the first period and human growth hormone in the second, and it showed a weak correlation in the third period with body mass and BMI. The lack of interactions between irisin level and other variables practically excludes its use in monitoring cyclist training. Future research would be complemented by the assessment of stress and postexercise changes in the cyclists’ macrocycle and expanding the research group to other athletes, including women.