The aim of this study was to analyse the level of severity of major depression and its relation to functioning and health-related quality of life over time in patients treated for their first episode of major depression. Thirty-three adult patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depression were included in the study. Semi-structured interviews and self-assessment questionnaires were used at baseline and at 6-monthly intervals in a 2-year follow-up, in order to measure the level of severity of depression, functioning and quality of life. The results showed that the first episode of major depression was rated as severe in 43% of cases. Multiple domains of functioning as well as quality of life were strongly affected in patients at baseline, although the level of functioning increased significantly over the study period, as did quality of life, but not concurrently with the decrease in the level of severity of the depression. Psychosocial functioning is an important outcome measure related to major depression, which underlines the importance of separate evaluations initiated and conducted by mental health nurses in order to determine whether or not patients have actually achieved a state of health.