Depression is one of the widespread diseases whose etiology is still unclear. Dysregulation of the hypothalamic-pituitary-adrenal axis can be the cause of this illness which is concomitant with a high level of cortisol. For this reason, the purpose of the study was to estimate the influence of the selective serotonin reuptake inhibitors (SSRIs) therapy used in monotherapy and polypragmasy on cortisol level in saliva of depressed women. Cortisol was determined in saliva collected from 40 depressed patients treated with SSRIs. HPLC with UV detection was used for quantification of cortisol after its extraction with dichloromethane. For statistical evaluation of the data, the cluster analysis and principal components analysis were used. Results of the study have shown that the SSRIs treatment reduces the cortisol level in saliva. The therapy with sertraline and polypragmasy had a strong influence on suppressing the cortisol secretion. Besides, the amplitude of changes of the cortisol level during the treatment had an impact on the duration of hospitalization. In conclusion, it can be stet that the process of reduction of the cortisol level is multiphasic and that the combination treatment had a stronger influence on suppressing the cortisol secretion than did antidepressants used in monotherapy.