Background: There is a lack of studies seeking to elucidate the association of religiousness with quality of life, comparing sick and healthy people, regardless the type of disease and age group. Objective: To examine the association between: (1) presence of a chronic health condition and the importance given to spirituality/ religiousness/personal beliefs (SRPB); (2) presence of a chronic health condition and quality of life (QOL) adjusted for age, socioeconomic level and depressive symptoms; (3) QOL and importance given to SRPB, also adjusted for the same factors. Design: cross-sectional study. Participants: n = 241 consisted of 122 inand outpatients from a university hospital and 119 religious healthy subjects from community. Measurements: a) WHOQOL-100 (QOL); b) BDI (depressive symptoms); c) WHOQOL-SRPBi -scale of importance assigned to the facets of the Spirituality/Religiousness/Personal Beliefs Module of WHOQOL-100 to measure importance given to religiousness. Results: Patients in comparison to healthy subjects showed worse scores in most WHOQOL-100 domains. The patients' mean score of the WHOQOL-SRPBi was 97.2 compared to the healthy subjects' mean score = 92.9 (P = 0.03). After using a multiple regression model, the WHOQOL-SRPBi appears positively associated with the psychological, the social relationships, the environment, the SRPB domains and general QOL (beta = 0.17; beta = 0.12; beta = 0.11; beta = 0.72; beta = 0.10, respectively), when adjusted for age, SEL, BDI and the presence of a chronic health condition. Discussion: The more important is the SRPB for these people, the better is their QOL in most of their domains, independently of other factors involved. This finding may be taken into account when planning interventions to improve QOL of chronic health patients.