<p>Schizophrenia is a chronic, disabling neurocognitive disorder associated with functional, psychological and social burden. Existing patient-reported outcome measures (PROMs), for schizophrenia have largely been developed in non-Indian settings and may not fully capture the lived experiences, contextual realities, and culturally relevant burden constructs of people receiving care in Tamil Nadu. This study aimed to develop and preliminarily evaluate a context-specific Schizophrenia Disease Burden Scale (SDBS) grounded in qualitative inquiry and tailored to Tamil Nadu. A mixed-methods design was adopted. Items were generated through a qualitative in-depth interview with individuals diagnosed with Schizophrenia (<i>n</i> = 10), followed by content validation by an expert panel (<i>n</i> = 11). The resulting questionnaire was administered to 325 participants by initial consecutive sampling followed by snowball sampling. Exploratory factor analysis (principal component analysis with varimax rotation) was performed to identify underlying domains, and internal consistency was assessed using Cronbach’s alpha. The initial version of the 65-item scale demonstrated good content validity (S-CVI = 0.87) and high internal consistency (Cronbach’s alpha = 0.922). Following the item reduction, a 24-item instrument was obtained with acceptable sampling adequacy (Kaiser-Meyer-olkin value = 0.744) and internal consistency of 0.910. Six domains were identified through exploratory analysis. Confirmatory factor analysis was performed as a preliminary internal structural assessment; however, independent validation is required. The SDBS provides a culturally relevant measure of disease burden that incorporates context-specific domains such as family support, social participation and socio-economic challenges. This initial validation supports its potential utility in Indian settings; however, further studies are required to establish external validity, test-retest reliability and broader applicability across diverse populations.</p>