Background: Sleep disorders are common in hemodialysis (HD) patients. This study examined the relationship between quality of sleep (QoS) and religious/spiritual activity in HD patients. Methods: The study subjects were 861 HD patients from 14 dialysis clinics in Taiwan. QoS and religious/spiritual activity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Royal Free Questionnaire respectively. Results: There was no difference in clinical parameters between the good and poor sleepers. Although total scores of religious and spiritual activity did not correlate with global PSQI score, patients who held strong ‘spiritual’ beliefs reported more problems in ‘sleep disturbances’, while those who exercised religious beliefs more strongly reported less trouble in ‘daytime dysfunction’. Conclusion: There is no significant correlation between QoS and religious/spiritual activity globally. However, the spiritual and religious activity did associate with different components of QoS.