Although many quality of life (QOL) scales have been developed, comparison of specific QOL instruments is lacking. We compared the psychometric properties of two QOL measures in parallel samples of mentally disturbed and non-patient subjects. We simultaneously administered the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and self-report items of the Lancashire Quality of Life Profile (LQOLP) to 199 patients with severe mental disorders and 175 non-patients. The patients were evaluated with psychiatric rating scales. We identified five concordant domains, and five instrument-specific domains for the LQOLP and four for the Q-LES-Q. The Q-LES-Q provides better psychometric properties than the LQOLP in both samples. Both instruments show a good capacity to evaluate QOL and discriminate between the patients and non-patient controls. Within the patient sample, both QOL measures showed similarly negative correlations with severity of depression, but not mania, positive, negative, and general symptomatology. Both instruments proved to be mental health related, but neither was mental-disorder specific. Despite the acceptable psychometric properties and correlation of general QOL indices, similar QOL domains proved to be instrument specific and not sufficiently compatible. These discrepancies should be considered when comparing evaluations from similar domains in these QOL scales.