Purpose: Nursing research studies investigating the relationship between spiritual wellbeing and health-related quality of life are lacking among Arab hemodialysis patients in Jordan or any other Arab country. The purpose of this study was to explore the associations between spiritual wellbeing, its religious and existential wellbeing dimensions, and health-related quality of life among Jordanian Muslim hemodialysis patients. Design: A cross sectional, quantitative correlational study. Methods: A convenience sample of 150 Jordanian hemodialysis patients completed a structured, self-administered questionnaire. Descriptive, bivariate, and multivariate regression models were used. Findings: The Jordanian hemodialysis patients had a moderate level of spiritual wellbeing and religious wellbeing, a low level of existential wellbeing, and a poor health-related quality of life. The findings revealed a significant moderate positive correlation between the spiritual wellbeing and its dimensions, and health-related quality of life. The existential wellbeing was the strongest predictor, with a large, positive, and significant effect after controlling for other spiritual, demographic and medical-related variables. Conclusion: Overall, the study suggests Jordanian hemodialysis patients use their religious and spiritual beliefs and practices as a coping mechanism, especially as sources of satisfaction, peace, comfort, strength and support, to help improve their health-related quality of life.