Objective: Investigating the relation between social isolation and cognitive function will allow us to identify components to incorporate into cognitive interventions. Method: Data were collected from 267 Appalachian older adults (M = 78.5, range 70–94 years). Overall cognitive functioning and specific cognitive domains were assessed from data of a self-assembled neuropsychological battery of frequently used tasks. Social isolation, social disconnectedness, and perceived isolation were measured from the Lubben Social Network scale-6. Results: Results indicated a significant positive association between all predictor variables (e.g., social isolation, social disconnectedness, and perceived isolation) and outcome variables (e.g., overall cognitive function, memory, executive functioning, attention, and language abilities). Perceived isolation accounted for nearly double the amount of variance in overall cognitive functioning than social disconnectedness (10.2% vs. 5.7%). Discussion: Findings suggest that social isolation is associated with poorer overall cognitive functioning and this remains true across varied cognitive domains.