Growing research has demonstrated a link between spiritual well-being and better health; however, little is known about possible physiological mechanisms. In a sample of highly religious healthy male and female adults (n = 100) ages 19-59 (m = 28.28) we examined the influence of spiritual well-being, as measured by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-Ex), on physiological risk factors for heart disease. Specifically we examined 24-h ambulatory blood pressure (BP), inflammation (hs-C-reactive protein), fasting glucose, and blood lipids. Regression analyses reveal that higher levels of spiritual-wellness (total FACIT-Sp-Ex score) was significantly related to lower systolic ambulatory BP (β = -.345; P < .001), diastolic ambulatory BP (β = -.24; P = .02), hs-C-reactive protein (β = -.23; P = .04), fasting glucose (β = -.28; P = .006), and marginally lower triglycerides (β = -.21; P = .09) and VLDL (β = -.21; P = .10) controlling for age, gender, and church attendance. Results remained generally consistent across the Meaning, Peace, Faith and Additional Spiritual Concerns subscales of the FACIT-Sp-Ex. Spiritual well-being may be cardio protective.