This chapter explores the pervasive experience of loneliness among adults with serious mental illness (SMI), a population at a particularly high risk of experiencing loneliness and social isolation. The chapter begins by defining loneliness and SMI, highlighting the detrimental effects of loneliness, and its high prevalence in individuals with SMI. Using a multi-level framework, the authors synthesize the personal, sociocultural, and environmental factors that contribute to loneliness. These include psychiatric symptoms, internalized stigma, childhood trauma, social cognition, loss of social roles and social support, and barriers related to transportation and housing. Subsequently, the chapter explores the impacts of loneliness on treatment outcomes, service utilization, physical health, and quality of life. A comprehensive review of interventions identifies promising strategies, including cognitive-behavioral therapies, social skills training, peer and community-based programs. Despite emerging evidence, mental health stigma, financial hardship, and systemic barriers may continue to limit intervention reach and sustainability. Therefore, the chapter concludes by emphasizing the need for integrated, multi-faceted approaches that facilitate both internal and structural changes and empower communities to reduce loneliness and improve well-being.