BACKGROUND: Anxiety and depression are common in seriously ill patients and may be associated with spiritual concerns. Little research has examined how concerns in different domains of spirituality are related to anxiety and depression. OBJECTIVE: To examine the association of spiritual history and current spiritual well-being with symptoms of anxiety and depression in patients with advanced illness. METHODS: Cross-sectional cohort study METHODS: Two hundred and ten patients with advanced illness, of whom 1/3 were diagnosed with cancer, 1/3 COPD, and 1/3 CHF. The mean age of the sample was 66 years, and 91% were Christian. METHODS: Outcome measures were the Profile of Mood States' Anxiety Subscale (POMS) and 10-item Center for Epidemiologic Studies Depression Scale (CESD). Predictors were three subscales of the Spiritual History Scale measuring past religious help-seeking and support, past religious participation, and past negative religious experiences and two subscales of the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale measuring the role of faith in illness and meaning, peace, and purpose in life. We conducted multiple regression analyses, controlling for demographics, disease type and severity, self-rated religiousness/spirituality, and frequency of religious attendance and devotion. RESULTS: In adjusted analyses, greater spiritual well-being, including both beliefs about the role of faith in illness and meaning, peace, and purpose in life were associated with fewer symptoms of anxiety (P ≤ 0.001) and depression (P