Introduction: Job stress is considered as an integral part of work environments that always affects people's job aspects and can reduce the performance and productivity of employees in organizations. The aim of this study was to investigate the relationship between job stress and job performance in staff of Yazd University of Medical Sciences. Methods: The study method was cross-sectional-analytical. Staff were considered a statistical population. The sample size was estimated at 282 people. The study used two standard questionnaires, Philip L. Rice's (1992) job stress and Patterson's job performance. Data analysis was performed by SPSS software. Results: 242 employees participated in this study. 42.1% of the respondents were men and 57.9% were women. The Deputy for Management and Resource Development (22.7%) and the Deputy for Social Development (5.4%) had the highest and lowest number of participants, respectively. Job stress was achieved in high-level staff and low-level job performance. Also, the relationship between job stress and job performance was found to have a significant inverse relationship (R = -0.318). Conclusion: In order to increase employee job performance and reduce stressors, senior university administrators need to improve the work environment by improving communication and interpersonal relationships. Applying proper human resource management and social and motivational support, improving facilities and planning to provide appropriate physical conditions in the workplace can also play an important role.