Introduction: Although many homebound older adults cope well using various resources, including religious coping strategies, some experience prolonged and unresolved psychosocial distress resulting in biological disruptions, such as hypercortisolism and increased inflammation, which are suggested mechanisms of decreased executive function. Purpose: To examine relationships of religious coping, psychosocial factors (stress, depression, loneliness), salivary biomarkers (cortisol, C-reactive protein (CRP), Interleukin-1β), and executive function. Methods: Data were collected cross-sectionally from 88 older adults (mean age 75.3). Religious coping, stress, depression, loneliness, and cognitive function were measured with standardized instruments, and saliva samples were collected for salivary cortisol, CRP, and IL-1β. Results: Negative religious coping significantly and positively correlated with stress, depression, and loneliness (r = 0.46, r = 0.21, r = 0.47, all p < 0.05); positive religious coping significantly and negatively correlated with depression and loneliness (r =´0.29, r =´0.23, both p < 0.05); and greater loneliness significantly predicted greater CRP (p < 0.05). For executive function, IL-1β showed a significant positive correlation (r = 0.23, p = < 0.05). Discussion: Our findings fill gaps related to biobehavioral interactions of religious coping and cognitive health in the aging population. Future research should include additional psychosocial and biobehavioral variables in larger samples of diverse and vulnerable populations. Collective findings may be able to identify particularly vulnerable subgroups of population, ultimately with tailored interventions to prevent cognitive decline.