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Background Prior studies of physical functioning after critical illness have been mostly limited to survivors of acute respiratory distress syndrome. The purpose of this study was to objectively assess muscle strength and physical functioning in survivors of critical illness from a general ICU and the associations of these measures to health-related quality of life (HRQL), mental health and critical illness variables. Methods This was a prospective cohort study of 56 patients admitted to a medical ICU (length of stay ≥4 days) from April 1, 2009, and March 31, 2010. Patients were assessed in clinic at 3 months post-hospital discharge. Muscle strength and physical functioning were measured using hand-held dynamometry and the 6-min walk test. HRQL was assessed using the short-form 36 (SF-36) and EuroQol-5D (EQ-5D) questionnaires. Results Three months post-hospital discharge, median age- and sex-matched muscle strength was reduced across all muscle groups. The median 6-min walk distance was 72 % of predicted. Physical functioning was associated with reductions in self-reported HRQL (SF-36, EQ-5D) and increased anxiety. Univariate regression modeling showed that reduced muscle strength and 6-min walk distance were associated with sepsis but not ICU length of stay. Multivariate regression modeling showed that sepsis and corticosteroid use were associated with a reduced 6-min walk distance, but again ICU length of stay was not. Conclusions Survivors of critical illness have reduced strength in multiple muscle groups and impaired exercise tolerance impacting both HRQL and mental health. These outcomes were worsened by sepsis and corticosteroid use in the ICU but not ICU length of stay. Interventions to minimizing the burden of sepsis in critically ill patients may improve long-term outcomes.