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Objectives: Stroke patients often experience poor sleep quality and spiritual health due to complications and limitations. In this situation, implementing spiritual care may reduce these problems. Therefore, this study aimed to examine the effect of a spiritual care program on sleep quality and spiritual health of Muslim stroke patients. Methods: This was a two-group randomized clinical trial conducted in Hamadan, Iran, in 2021, with 117 stroke patients. The samples were selected by convenience sampling and assigned to experimental (N = 59) and control (N = 58) groups based on random permutation blocks. The data were collected using the demographic information form, the Pittsburgh Sleep Quality Index, the Paloutzian and Ellison Spiritual Well-Being Scale, and the Modified Rankin Scale before and one month after the intervention. The experimental group received five daily sessions of spiritual care for 45–60 min based on standard and local methods, including patient orientation and identification of spiritual needs, religious care, supportive spiritual care, and beneficial evaluations. Data were analyzed by chi-square test, Fisher's exact test, independent t-test, and paired t-test at 0.05 significance level in SPSS 21. Results: The socio-demographic characteristics were similar between the groups (p > 0.05). At baseline, there was no significant difference in sleep quality and spiritual health between the experimental and control groups (p > 0.05). However, after the intervention, the sleep quality and spiritual health of patients in the experimental group improved significantly compared with the control group (p < 0.05). Conclusion: The spiritual care program improved sleep quality and spiritual health of stroke patients; therefore, nurses should consider these aspects to provide holistic care.