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We investigated the relationships between physical isolation at home during the period when many US states had shelter-in-place orders and subsequent longitudinal trajectories of depression, anxiety, and loneliness in older adults over a 6 month follow-up.Data were from monthly online questionnaires with US adults aged ≥ 55 in the nation-wide COVID-19 Coping Study (April through October 2020, N = 3978). Physical isolation was defined as not leaving home except for essential purposes (0, 1-3, 4-6, and 7 days in the past week), measured at baseline (April-May). Outcomes were depressive symptoms (8-item Center for Epidemiological Studies Depression Scale), anxiety symptoms (5-item Beck Anxiety Inventory), and loneliness (3-item UCLA loneliness scale), measured monthly (April-October). Multivariable, population- and attrition-weighted linear mixed-effects models assessed the relationships between baseline physical isolation with mental health symptoms at baseline and over time.Physical isolation (7 days versus 0 days in the past week) was associated with elevated depressive symptoms (adjusted β = 0.85; 95% CI 0.10-1.60), anxiety symptoms (adjusted β = 1.22; 95% CI 0.45-1.98), and loneliness (adjusted β = 1.06; 95% CI 0.51-1.61) at baseline, but not with meaningful rate of change in these mental health outcomes over time. The symptom burden of each mental health outcome increased with increasing past-week frequency of physical isolation.During the early COVID-19 pandemic, physical isolation was associated with elevated depressive symptoms, anxiety symptoms, and loneliness, which persisted over time. These findings highlight the unique and persistent mental health risks of physical isolation at home under pandemic control measures.