Abstract: OBJECTIVES: Loneliness is a pervasive public health problem, especially among individuals with problematic substance use (PSU). To date, however, scarce research has examined the prevalence and correlates of loneliness in vulnerable segments of the population, such as US military veterans. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US veterans. The Three-Item Loneliness Scale was used to assess clinically significant loneliness (≥6). Multivariable logistic regression and relative importance analyses were conducted to identify correlates of loneliness in 593 veterans with PSU. RESULTS: Nearly half of US veterans with PSU (47.4%) reported clinically significant loneliness. In a multivariable analysis, loneliness was independently associated with being unmarried/unpartnered, greater current psychological distress (depressive and posttraumatic stress symptoms), lifetime suicide attempt, and physical disability, smaller social network size, and lower levels of purpose in life and optimism. In a relative importance analysis, major depressive and posttraumatic stress symptoms (35.4%), smaller social network size (16.7%), and lower purpose in life (15.0%) and optimism (13.6%) explained the majority of the variance in loneliness. Purpose in life also moderated the link between depressive symptoms and loneliness: among veterans with depressive symptoms, those with higher purpose in life had a lower likelihood of loneliness. CONCLUSIONS: Nearly half of US veterans with PSU report significant loneliness. Prevention and treatment strategies that address psychological distress, foster meaningful social connections, and enhance veterans' sense of purpose may help mitigate the burden of loneliness in this population.