Objective: To examine whether job burnout is associated with health-related quality of life (HRQOL) in employees with cardiovascular disease. Methods: In this longitudinal study, we included 305 female hospital nurses with cardiovascular disease. Job burnout was measured by the 6-item Copenhagen Burnout Inventory at baseline. We categorized study participants into low, intermediate and high levels of job burnout based on tertiles. HRQOL at baseline and at oneyear follow-up was operationalized in terms of the physical and mental functioning summary scores of the short form 8-item health survey (SF-8), which is an abbreviated version of the widely used SF-36 with score ranges of 0-100. Linear regression was applied to examine longitudinal associations. Results: After taking into account relevant socio-demographic, behavioral, and work-related covariates as well as HRQOL scores at baseline, we found that both physical functioning and mental functioning declined (by 2.53 points and 3.02 points respectively, p < 0.05) in the high job burnout group compared with the low job burnout group. Dose-response relationships were also observed (p < 0.05). Conclusion: Job burnout predicts decline of HRQOL one year later among employees with cardiovascular disease.