The purpose of this mixed-method study was to better understand how social isolation and support would be associated with depression among older adults in rural areas in the U.S. during the COVID-19 pandemic. A total of 103 participants completed a Qualtrics survey. As hypothesized, the hierarchical regression findings indicated that depressive symptoms were positively associated with social isolation and were negatively associated with only social support from significant others. Five interviews were analyzed by themes including social isolation, technology use and social connectivity/support, and depression. The findings of this study provide insights and useful information for practitioners to develop effective services.