This study aimed to investigate 1) the relationship between subjective perception of quality of life (QoL) and clinician-rated levels of psychosocial functioning and 2) the relationship of these indicators with neuropsychological performances, in a sample of 117 subjects with mood and anxiety disorders hospitalized for a 4-week psychiatric rehabilitation program. At the beginning of the hospitalization, QoL and clinician-rated functioning were respectively measured by the World Health Organization Quality of Life Assessment-Brief Form (WHOQOL-BREF) and the Global Assessment of Functioning (GAF) scale, and subjects were administered a neuropsychological battery evaluating verbal and visual memory, working memory, attention, visual-constructive ability, language fluency and comprehension. We did not find any association between WHOQOL-BREF and GAF scores and between cognitive impairment and lower QoL or clinician-rated functioning. Our results suggest that 1) the individuals' condition encompasses different dimensions that are not fully captured by using only clinician-rated or self-administered evaluations; 2) the GAF scale seems unable to indicate the cognitive impairments of our subjects and the WHOQOL-BREF does not appear to be influenced by these deficits. Overall, our findings suggest the need of simultaneously use of multiple assessment tools, including objective evaluations of functioning and different measures of QoL, in order to obtain a more complete clinical picture of the patients. This may allow to identify more specific targets of therapeutic interventions and more reliable measures of outcome.