The correlations between depression and stress are quite accepted nowadays, as well as the fact that cortisol levels could also represent fundamental risk factors for major depressive disorder. However, when it comes to the modifications of cortisol levels in depression, the results are controversial. Same goes for the cortisol modifications in irritable bowel syndrome (IBS), which is a functional digestive disorder characterized by a strong biopsychological component, being highly influenced or exacerbated by stressful stimuli. Thus, in the present report we were interested in seeing if there are any serum cortisol levels variations in patients with depression and irritable bowel syndrome, by looking at cortisol modifications in two different groups of patients: a control group with major depression disorder and another study group composed by major depression disorder + IBS patients. Thus, our data presented here are suggesting that there is a significant increase in cortisol levels in the morning serum of the patients with major depression disorder + IBS, as compared to the group having only depression. The results presented here could have an important relevance in the context of managing the stress-related factors in the pathological entities described above.