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Abstract Background Digital mental health interventions (DMHIs) may reduce treatment access issues for those experiencing depressive and/or anxiety symptoms. DMHIs that incorporate relational agents may offer unique ways to engage and respond to users and to potentially help reduce provider burden. This study tested Woebot for Mood & Anxiety (W-MA-02), a DMHI that employs Woebot, a relational agent that incorporates elements of several evidence-based psychotherapies, among those with baseline clinical levels of depressive or anxiety symptoms. Changes in self-reported depressive and anxiety symptoms over 8 weeks were measured, along with the association between each of these outcomes and demographic and clinical characteristics. Methods This exploratory, single-arm, 8-week study of 256 adults yielded non-mutually exclusive subsamples with either clinical levels of depressive or anxiety symptoms at baseline. Week 8 Patient Health Questionnaire-8 (PHQ-8) changes were measured in the depressive subsample (PHQ-8 ≥ 10). Week 8 Generalized Anxiety Disorder-7 (GAD-7) changes were measured in the anxiety subsample (GAD-7 ≥ 10). Demographic and clinical characteristics were examined in association with symptom changes via bivariate and multiple regression models adjusted for W-MA-02 utilization. Characteristics included age, sex at birth, race/ethnicity, marital status, education, sexual orientation, employment status, health insurance, baseline levels of depressive and anxiety symptoms, and concurrent psychotherapeutic or psychotropic medication treatments during the study. Results Both the depressive and anxiety subsamples were predominantly female, educated, non-Hispanic white, and averaged 38 and 37 years of age, respectively. The depressive subsample had significant reductions in depressive symptoms at Week 8 (mean change =—7.28, SD = 5.91, Cohen’s d = -1.23, p |