Growing diversity in the workforce has compelled scholars and managers to create inclusive organizational environments for employees who belong to marginalized groups. Yet, little is known about how employees with stigmatized medical conditions manage their job demands. In this article, we examine the role of stigma associated with human immunodeficiency virus (HIV) in shaping the ability of employees with HIV to contribute to their organizations. Drawing on stigma and emotions literatures, we investigate the influence of HIV stigma on job effectiveness (i.e., in-role performance and organizational citizenship behaviors) through the mediated paths of fear and shame. We further examine whether a psychological (i.e., core self-evaluation [CSE]) and a physiological (i.e., CD4 cell count, defined as the biological indicator of HIV severity) factor would moderate these mediating relationships at the first and second stages, respectively. Using a sample of 225 employees with HIV surveyed across three measurement periods with a time lag of 3 months, we found support for the dual-stage moderated mediation model linking HIV stigma and job effectiveness via shame under lower (vs. higher) levels of CSE and CD4 cell count. By contrast, we did not find evidence for the mediating role of fear. Implications of our findings for theory and practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).