The first objective of the current observational study was to assess the degree of religiosity in Greek Christian Orthodox primary caregivers of patients with multiple sclerosis (MS). The second objective was to evaluate the interrelations between religiosity and quality of life (QOL) and to identify the determinants of QOL, an endpoint of considerable importance in clinical research and practice. Twenty-two male and 13 female primary caregivers (mean age 47.3 ± 12.4 years) of an equal number of patients with MS, who consented to participate, completed the Systems of the Greek version of the Belief Inventory (SBI-15R) and the Greek validated version of EuroQOL (EQ-5D). The analysis revealed high scores on religiosity, especially among females. Caregivers scored in the religious beliefs and practices subscale of SBI-15R with a mean score of 22.8 ± 7.8 (range 0-30) and with 7.1 ± 4.8 (range 0-14) in the social support subscale. However, both of the SBI-15R domains were almost unrelated to the degree of overall QOL. There was only a reliable (but with little clinical value) association between the pain/discomfort domain of the EQ-5D with the SBI-15R beliefs and practices subscale (r = -0.38, p = 0.03). Although high levels of religiosity among Greek Christian Orthodox primary caregivers of MS patients were evident, this study did not demonstrate any beneficial effect of religious beliefs and practices on their QOL. Further prospective studies with a population with the same and/or diverse religious and cultural backgrounds are needed to better elucidate the complex association between religiosity and QOL in primary caregivers of MS patients.