The students’ cortisol levels reflecting stress are associated with the anxiety and depression manifestations, which is important in terms of the educational process hygienic optimization. The study aimed to assess the correlation on students’ blood levels of cortisol with anxiety and depressive conditions at various stages of training. A total of 200 1^st-year students, who were taught during the academic year 2023–2024, took part in the comparative cross-sectional study. Serum cortisol levels were determined by enzyme immunoassay (ELISA), and the HADS scale was used to detect anxiety and depressive disorders. Signs of anxiety depression at training stages were detected in 34.4–43.6% (р = 0.189) and 18.2–24.7% (р = 0.256) of students. In the end of the academic year the share of clinical form in the structure of anxiety increased by 19.3% and that in the structure of depression increased by 4.3%.  The cortisol levels associated with anxiety were higher in spring, than on autumn ― 32.3% (р = 0.001), including 35.3% with subclinical form (р = 0,001), 28.4% with clinical form (р = 0.028); the values associated with depression were 53.9% higher in spring (р = 0,001), including 55.4% with subclinical form (р = 0.001), 45.6% with clinical form (р = 0.052). There was no association of cortisol levels with anxiety in autumn (r = 0.07, р = 0.488), there was a moderate positive one in spring (r = 0.51, p = 0.001), including the following: girls in autumn had r = 0.03, р = 0.771, in spring r = 0.49, р < 0.001, while boys in autumn had r = 0.18, р = 0.296, in spring r = 0.57, р = 0.001, respectively. A nonlinear log model showed a significant effect of anxiety (F = 16.26, p < 0.001), explaining 7.7 % of variance. The findings are important for the development of preventive programs focused on stress management in students.