Background: Among patients with schizophrenia, there is evidence of a negative association between self-stigma and subjective quality of life (SQoL), and self-esteem was an important mediator in the association. We attempted to use a longitudinal study to investigate the aforementioned mediation on a sample with schizophrenia. Methods: We used longitudinal data retrieved from medical records of a psychiatric centre between June 2014 and December 2015. In the data, we retrieved information of self-stigma using the Self-Stigma Scale — Short; SQoL, using the WHO questionnaire on the Quality of Life — Short Form; and self-esteem, using the Rosenberg Self-Esteem Scale. All the measures were evaluated five times. Linear mixed-effect models accompanied by Sobel tests were used to tackle the mediating effects. Results: Data from 74 patients (57 males) with schizophrenia were eligible for analysis; their mean ( SD) age was 39.53 (10.67); mean age of onset was 22.95 (8.38). Self-esteem was a mediator for patients in physical ( p = .039), psychological ( p = .003), and social SQoL ( p = .004), but not in environment SQoL ( p = .051). Conclusion: Based on our findings, mental health professionals could tailor different programs to patients with schizophrenia, such as self-stigma reduction and self-esteem improvement programs. However, treatment as a whole should be sensitive to both self-stigma and self-esteem. Also, we should consider individuals’ health and wellbeing from social perspectives of disability rather than the medical model of disability emphasising symptoms and medications.