Background. Metabolic changes induced by combined oral contraceptives (COC) use is regularly active in females. Objectives. Analyzing blood cortisol and other biochemical variables in active (COC) users and non-users. Methods. A total of 123 active female students (25 COC users and 98 non-users) volunteered to participate in the study. The COC users declared 2-3 years of using different types of combined the fourth generation COC pills. In all participants' body composition, physical activity and dietary habits were determined. Circulating cortisol and insulin were determined using standard radioimmunoassay techniques. Plasma glucose and lipoproteins were determined using colorimetrical methods. To evaluate the health risk ratio of total cholesterol to HDL-cholesterol (Castelli index I) and LDL-cholesterol to HDL-cholesterol (Castelli index II) were calculated. Results. There were no between-groups differences in body composition and dietary habits. The COC users had markedly elevated plasma cortisol (p < 0.001), triacylglycerols (TG) (p < 0.001), total cholesterol (TC) (p < 0.002) and HDL-C (p < 0.040) with no effect on glucose, LDL-cholesterol (LDL-C) and TC-to HDL-C ratio. In contrast, the LDL-C to HDL-C ratio in COC users was lower vs. non-users (p < 0.002). COC users were characterized by a higher frequency of elevated TC (p < 0.001) and HDL-C (p < 0.040). However, in all participants Castelli index I and II were within the accepted limits suggesting a low risk of cardiovascular disease. Conclusion. In COC users regular physical activity does not prevent changes in circulating biochemical variables, however, these changes did not affect cardiovascular risk which is low and similar to that noted in active non-users.