This study aimed to investigate the influence of organization-based self-esteem (OBSE) on employee well-being in the macro context of the social exchange relationship between employee and organization. We recruited participants by using an Internet research company with a research panel of approximately one million members nationwide. A web-based questionnaire survey was conducted, and 1,127 responses were collected [employees from a variety of organizations, 49.1% female, mean age 39.58 (SD=10.4, range 20-60), mean tenure 10.96 years (SD=9.75, range 0-41), 65.3% non-managers]. OBSE, perceived organizational support (POS), perceived supervisor support (PSS), and employee well-being, consisting of work engagement (WE), depressive symptoms (DE), and somatic complaints (SO) were measured. Structural equation modeling (SEM) demonstrated that POS was positively related to OBSE, and in turn OBSE was positively related to WE and negatively related to DE and SO. In addition, POS was directly related to WE. SEM also indicated that POS fully mediated the relationship between PSS and OBSE. This study constitutes preliminary work demonstrating a positive effect of OBSE on employee well-being in the context of social exchange in the employee-organization relationship. Longitudinal studies are required in order to gain better knowledge of the causal relationships among the variables in this study.