This cross-sectional study examines the relationships of loneliness and depressive symptoms to thoughts of self-harm among a clinical sample (n = 150) of older adults (M = 58.42 years, SD = 5.86 years; male, 55.3%; African American, 61.3%) with serious mental illness (SMI) receiving publicly funded, community-based psychiatric rehabilitation services. Participants completed the De Jong Gierveld Loneliness Scale, Multidimensional Scale of Perceived Social Support, Patient Health Questionnaire 9, and Geriatric Depression Scale–Short Form. Mediation analyses tested the association of loneliness with thoughts of self-harm through depressive symptoms and were adjusted for social support and demographic variables. The direct association of loneliness with thoughts of self-harm was mediated by depressive symptoms; indirect associations of overall and emotional loneliness to thoughts of self-harm were significant. Findings suggest the need for clinicians to reduce feelings of loneliness among older adults with SMI as a means of partially ameliorating depressive symptoms and thoughts of self-harm.