OBJECTIVES: This study assesses the validity and responsiveness over changes of the English version of the S-QoL, first schizophrenia-specific health-related quality of life scale developed from patients' viewpoint on the need-based framework. METHODS: The S-QoL, comprising 41 items exploring eight dimensions (Psychological Well-being, Self-esteem, Relations with Family, Relations with Friends, Resilience, Physical Well-being, Autonomy and Sentimental Life), was first developed and validated in French. After a standard backward-forward translation process, its English version was tested in a sample of patients with schizophrenia. Two assessments were performed: baseline and 12 weeks later. Psychometric properties (validity and sensitivity over changes) were evaluated using methods from Classical Test Theory, Rasch analyses and structural equation modelling. RESULTS: A total of 128 patients filled-in the S-QoL. The factorial structure of the original version was globally retrieved. The questionnaire was well accepted (missing dimension rates lower than 3%). Cronbach's alphas were greater than 0.70 for 6 of the 8 dimensions. The S-QoL dimensions and total score were statistically correlated with depression assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and severity of symptoms measured by the Positive and Negative Symptoms Scale (PANSS). Using the sub-sample of patients rated “Very much Improved” or “Improved” on the Clinical Global Impression of Improvement (CGI-I) at Week 12, all the dimensions and the total score were statistically significantly improved. Five of the dimensions, as well as the total score, reached an effect size of at least 0.50 indicating an at least moderate change on health status. CONCLUSION: These results strengthen the usefulness of assessing the impact of schizophrenia on patients' everyday life with the S-QoL, specifically designed for assessing the health-related quality of life of patients with schizophrenia. Its sensitivity to changes in health state is of major interest for evaluative purposes.