OBJECTIVE: To evaluate the relationship between S/R, demographic data, and clinical variables of Brazilian adult patients with epilepsy (PWE). METHODOLOGY: The scores of the WHO Quality of Life for Assessment of Spirituality, Religion, and Personal Beliefs (WHOQOL-SRPB) were related to demographic and clinical aspects, the Spirituality Self-Rating Scale (SSRS), and the Spiritual/Religious Coping Scale (SRC) of 60 PWE. RESULTS: The mean age was 42.8y and 35 (58.3%) patients reported regular religious practice. In the WHOQOL-SRPB, greater inner peace and harmony were observed in women, greater wholeness and integration, hope and optimism in married patients, and greater spiritual connection in patients with religious practice. The use of polytherapy with antiseizure medication (ASM) was associated with lower spiritual connection, wholeness, integration, and S/N in the WHOQOL-SRPB. The higher seizure frequency was associated with lower spiritual connection. Facet scores and total scores of the WHOQOL-SRPB were significantly correlated with positive and negative coping and a greater perception of spiritual guidance. CONCLUSION: In the PWE, the use of S/R differed according to gender, marital status, and religious practice. Clinical variables influenced the perception of S/R, which differed according to the use of ASM, frequency, and type of epileptic seizures. The greater use of coping and spiritual guidance was associated with different facets of S/R and personal beliefs.