Introduction The post-intensive care syndrome (PICS) encompasses multiple, diverse conditions, such as physical disability, cognitive impairment, and depression. We sought to evaluate whether conditions within PICS have similar associations with mortality among survivors of critical illness. Materials and methods In this retrospective cohort study, we identified 248 critically ill patients with intensive care unit stay [greater than or equal to]72 hours, who underwent PICS evaluation. Patients with disability in activities of daily living, cognitive impairment, or depression before hospitalization were excluded. We defined PICS using established measures of physical disability (usual gait speed), cognitive impairment (Mini-Cog test), and depression (Patient Health Questionnaire-2) at hospital discharge. The endpoint was all-cause mortality. Results Patients had a median age of 69 years and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 16. One hundred thirty-two patients were classified as having PICS, and 19 patients died. 81/248 (34%) patients had physical disability, 42/248 (19%) had cognitive impairment, and 44/248 (23%) had depression. After adjusting for covariates on multivariable Cox regression analyses, PICS was significantly associated with all-cause mortality (hazard ratio [HR] 3.78, 95% confidence interval [CI] 1.02 - 13.95; P = 0.046). However, the association between PICS and all-cause mortality was related to physical disability and cognitive impairment (P = 0.001 and P = 0.027, respectively), while depression was not (P = 0.623). Conclusion While PICS as a syndrome has been useful in gaining attention to the sequelae of critical illness, its relationship with long-term mortality is driven largely by physical disability and cognitive impairment and not depression.