Stroke is a disease that affects the arteries leading to and within the brain. Stroke usually creates a range of disabilities such as physical deficits and difficulty in performing daily activities. These long-term needs and the continuous caregiving sequence affect the care burden and spiritual well-being of caregivers. The correlational study population consisted of caregivers of stroke older patients (N = 100). Burden Interview Scale, Spiritual Well-Being Scale and Religious Coping Scale were used. Descriptive analyses, independent sample t-test, one-way analysis of variance, correlation, regression analyses were used to evaluate the data. The mean age of caregivers was 48.38 ± 13.52 years. The score of Burden Interview Scale was 31.41 ± 15.13 (light/moderate), Negative Religious Coping was 7.39 ± 3.17 (moderate), Positive Religious Coping was 24.30 ± 4.34 (high), and Spiritual Well-Being was 21.65 ± 6.73 (low). There is a significant relationship between Burden Interview and Negative Religious Coping (r = 0.274; P = 0.006), Burden Interview and spiritual well-being (r = -0.563; P = 0.000), and spiritual well-being and positive religious coping (r = 0.228; P = 0.026). The predictors that affect the spiritual well-being of caregivers were found to be Burden Interview (β = -0.571) and Positive Religious Coping (β = 0.181) (P < 0.05). Nurses play an important role in increasing the spiritual well-being levels and religious coping behaviours of caregivers. Nurses should communicate empathically with caregivers, understand their feelings, and provide emotional support.