Objectives Dementia is a common disease in the elderly and imposes a heavy care burden on family members. Many factors can be associated with care burden. One of these factors can be the caregivers' Spiritual Well-Being (SWB). This study aimed to examine the relationship between SWB and care burden in caregivers of dementia patients. Methods This correlational study was conducted on 60 caregivers (75% female and 25% male with a mean age of 47 years) of patients with dementia referred to Rasoul-e-Akram Hospital and Brain & Cognitive Clinics in Tehran, Iran in 2019. Samples were selected using purposive and convenience sampling methods. The caregivers were evaluated by using the Caregiver Burden Questionnaire and SWB Scale and a socio-demographic checklist. Data were analyzed by using Pearson's correlation coefficient and multiple linear regression analysis in SPSS software at the significance level of P<0.05. Results About 16.7% of caregivers had little care burden, 35% had moderate to severe burden, 25% moderate burden and 23.3% severe burden. Moreover, 1.7% had poor SWB, 66.7% moderate SWB and 31.7% high SWB. The care burden had a negative and non-significant relationship with religious dimension of SWB (r=-0.089, P=0.505), and a negative and significant relationship with existential dimension of SWB (r=-0.283, P=0.032). Linear regression model revealed that existential dimension had a relationship with care burden (beta=-0.298, P=0.023) and explained 9% of variation in care burden. Conclusion SWB plays an important role in improving the overall health of caregivers. in addition to being one of determinant of care burden, it acts as a factor in enhancing other aspects of health. Overall, caregiving is a stressful job; being aware of positive topics such as spirituality helps therapists provide strategies for caregivers to reduce their stress and care burden.