Objectives: The objectives of this work were to examine whether there is an increased activity of Hypothalamic Pituitary Adrenocortical (HPA) axis in major depressive disorder and schizophrenia patients, and to detect the presence of an association between the level of plasma cortisol and thoughts of death and anhedonia in both disorders.Methods: Twenty patients with major depressive disorder (MDD) and 20 patients with schizophrenia were studied in comparison to 20 controls ; all patients were assessed through Present State Examination 10th revision of the Schedules of Clinical Assessment in Neuropsychiatry (SCAN) (PSE-10). Snaith Hamilton Pleasure Scale (SHAPS) was used for all patients to assess anhedonia ; Beck's Suicidal Ideation Scale (SIS) was used for all patients to quantify and assess suicidal intention ; Beck’s Depressive Inventory (BDI) was used for depressed patients to assesses mood, cognitive, and somatic symptoms of depression ; the Positive and Negative Syndrome Scale (PANSS) was used for schizophrenic patients to assess positive and negative symptoms ; their relationship to one another and to global psychopathology. Blood samples will be collected from all patients to assess plasma cortisol level AM and PM. Results: There are increased levels of morning and evening cortisol in major depressive disorder and schizophrenia patients. Morning and evening cortisol levels are higher in schizophrenia than MDD patients. Thoughts of death are positively associated with elevated morning cortisol in schizophrenia and MDD patients. Anhedonia and suicide risk are relatively higher in MDD in comparison to schizophrenia.Conclusions: Major depressive disorder and schizophrenia patients have higher cortisol levels in comparison to control suggesting hyperactivity of HPA axis in both disorders. Anhedonia predicts suicidal tendencies in depression and schizophrenia ; the higher the anhedonia the higher the suicidal ideations were. Higher diurnal cortisol pattern in depression appears to signal a deviation of normal HPA axis and is related to greater negative affect and affective disturbance. There is reduction in synaptic plasticity due to insufficient neurotrophic action in schizophrenia.