Quality of life and loneliness are closely associated with mental and physical health outcomes. This relationship is particularly important in Veterans who experience elevated rates of disabilities, comorbidities, and chronic health conditions as compared with non-Veterans. In the present project, we use data from the Military Health and Well-Being Project (n = 1469, 67.2% men, 32.3% women, 0.5% transgender, nonbinary, prefer not to say) to investigate the link between five domains of quality of life (i.e., general quality of life, physical health, psychological health, social relationships, and environment) with loneliness in American Military Veterans. Findings indicated that every domain of quality of life was negatively and significantly associated with loneliness (r's < −0.45, p's < 0.001), such that quality of life decreased as loneliness increased. We further found, using linear regression, that quality social relationships (β = −0.385, t = −13.23), psychological functioning (β = −0.196, t = −5.28), and physical health (β = −0.133, t = −4.174) were related to low levels of loneliness. Taken together, these findings indicate that in this sample of Veterans 1) general quality of life, physical health, psychological health, social relationships, and environment are all strongly connected with loneliness, and 2) of these, social relationships, psychological health, and physical health seem to protect most against loneliness, with large robust effect sizes. We recommend that intervention and policy researchers continue to investigate and develop feasible, acceptable, and cost-effective ways to promote social relationships, psychological health, and physical health among Veterans. Data were collected during the COVID-19 pandemic, which may limit generalizability of these findings.