Abstract: Background/Objectives: The study's objective was to determine whether social isolation serves as a mediator in the cross-sectional relationship between food insecurity, both as a short-term and longer-term situation, with resource use and depressive symptoms as outcomes. Methods: This cross-sectional design study utilized secondary survey data, including 30-day and 12-month food security measured by the U.S. Household Food Security Survey Module. The Baron-Kenny mediation approach was used to determine whether social isolation mediated the relationship between food security, depressive symptoms, and resource use (p ≤ 0.05). Results: Social isolation mediates the association between both 30-day and 12-month food security with depressive symptoms but not resource use. Conclusions: Acknowledging and targeting social isolation, policies, and interventions that integrate peer support and community outreach to promote food security could support rural veterans food security and mental health.