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Background: Stroke can impact multiple levels of function and result in complex disability. Few studies have examined limitations across the range of functions from body function to social participation, or explored the impact of post-stroke comorbidities, such as depression, obstructive sleep apnea (OSA) and cognition, on function, especially in the long-term. We aimed to determine post-stroke predictors of multiple levels of functioning approximately 2 years after a stroke, and to specifically evaluate the impact of depressive symptoms, OSA and cognitive impairment on outcome.Hypothesis: We hypothesized that in addition to traditional predictors of outcome–age and stroke severity–depression, OSA and cognitive impairment will predict functional outcome in multiple domains.Methods: Baseline assessment of depression, apnea and cognitive impairment with 2-year follow-up assessment of functional outcome to evaluate each of the three levels of functioning as stated in the WHO International Classification of Functioning: Body Function (Montreal Cognitive Assessment), Activity (modified Rankin) and Participation (Reintegration to Normal Living Index).Results: A total of 162 patients were enrolled at approximately 2 years and 5 months post-stroke. Forty one percent had activity limitations, 58% were cognitively impaired and 68% had restrictions in participation. Long-term activity limitation was predicted by greater age (OR = 0.95), stroke severity (OR = 1.69) and cognitive impairment (OR = 1.28) at baseline. Body function impairment was predicted by greater age (OR = 0.96), and cognitive impairment (OR = 1.49). Participation restriction was predicted by cognitive impairment (OR = 1.26).Conclusion: Baseline cognition predicts long-term function in multiple domains and is a better predictor of long-term participation than age or baseline stroke severity. In view of the widespread impact of post-stroke cognitive impairment on every level of functioning, routine post-stroke cognitive screening and target interventions are warranted. Greater attention to functional domains beyond activity could further optimize recovery and enhance outcome after stroke.