Nursing home residents commonly experience depression. This study examined the relationship between contextual isolation (having a socially salient characteristic in a nursing home where few other residents share that characteristic) and diagnosed depression. Using a cross-sectional design, we identified 1,033,485 long-stay nursing home residents from the 2010-2019 national Minimum Data Set 3.0 (a resident-centered assessment) 1 year from admission. Sixteen percent were contextually isolated on multiple characteristics. Males who were multiply contextually isolated had diagnosed depression more than males without contextual isolation (adjusted prevalence ratio: 1.09; 95% Confidence interval: 1.08-1.10). Resident groups defined by racial group who were contextually isolated on multiple characteristics had a higher prevalence of diagnosed depression than those without contextual isolation. Interventions targeting the impact of contextual isolation may reduce the prevalence of diagnosed depression among long-stay nursing home residents.