Background: Women have unique health concerns in the context of chronic illness. Although health literacy has been linked to health-related quality of life, the pathway by which some factors mediate this relationship has not been well examined among Saudi women with chronic disease.

Purpose: This study was designed to examine the relationship between health literacy and health-related quality of life and determine the mediating roles of healthy lifestyle and patient-centered care in explaining this relationship.

Methods: A cross-sectional study was used. A random sample of 20 primary healthcare centers in Saudi Arabia was selected. A convenience sample of 300 women diagnosed with a chronic illness was recruited from these centers. Structural equation modeling was used to test the proposed relationships.

Results: Controlling for women's age and education, the hypothesized model adequately fit the data. Health literacy and its dimensions were found to positively and directly affect both patient-centered care (β = 0.614, B = 0.189, p < .001) and healthy lifestyle behaviors (β = 0.550, B = 1.211, p < .001). Furthermore, both patient-centered care (β = 0.390, B = 1.301, p < .001) and healthy lifestyle behaviors (β = 0.322, B = 0.150, p < .001) were found to positively and directly affect health-related quality of life, whereas health literacy had significant, direct (β = 0.285, B = 0.292, p < .001) and indirect (β = 0.417, B = 0.428, p < .001) effects on health-related quality of life through patient-centered care and healthy lifestyle behaviors.

Conclusions/Implications for Practice: Special consideration should be given to health literacy, patient-centered care, and healthy lifestyle behaviors to enhance health-related quality of life in women with chronic illness. Gender-specific health services and interventions are needed to improve women's health literacy.