OBJECTIVES: A disease's workplace impact on an employer is often highly sought but rarely available information that an employer can use to understand the value of a health intervention and to influence health insurance coverage of that intervention. This document presents a conceptual framework to analyze a disease's workplace impact on an employer. METHODS: The conceptual framework presented here was developed on the basis of a comprehensive literature review, extensive consultation process, analytical mapping of concepts, objects, behaviors, domains, functions, and relationships, as well as real case analyses. RESULTS: A four-component conceptual framework of workplace impact of a disease is proposed to guide researchers to quantify disease-workplace-impact from an employer perspective. These four components are work interruption costs, work care costs, worker turnover costs and productivity reduction costs. The examples of work interruption costs include employer-paid medical leaves, absence, short-term disability, and other forms of work interruption resulted from a disease. The examples of work care costs include disease related work adaptation costs, and a disease related insurance premium increase. The examples of worker turnover costs include worker separation costs, new worker recruitment costs, and new worker training costs. The productivity reduction costs are mainly the costs of productivity decrease resulted from presenteeism. Both predisposing factors and intervening factors of workplace impact are discussed in this conceptual framework. Based on this conceptual framework, we conducted a real world case analysis, which suggests not only significant workplace impact of a debilitating disease, but also some methodological challenges in estimating workplace impact of a disease from an employer's perspective. CONCLUSIONS: Our four-component conceptual framework can guide researchers to quantify workplace impact of a disease from an employer's perspective. The real case analysis suggests a debilitating disease not only affect patients, but also exert significant workplace impact on an employer.