OBJECTIVE: Sepsis often leads to heterogeneous symptoms of post-intensive care syndrome (PICS) composing physical, cognitive, and psychiatric disabilities, resulting in deteriorated quality of life (QoL), with limited interventions. This study aimed to identify phenotypes of sepsis-associated PICS by physical, cognitive, and psychiatric function and QoL at hospital discharge. DESIGN: A prospective observational study. SETTING: Twenty-one mixed ICUs. PATIENTS: All consecutive adult patients between November 2020 and April 2022, diagnosed with sepsis at ICU admissions and survived discharge, were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Phenotyping with clusters determined by three approaches was performed with following variables at hospital discharge: Barthel Index (≤ 90 defined physical PICS), Short Memory Questionnaire (<
40 defined cognitive PICS), Hospital Anxiety and Depression Scale (≥ 8 defined psychiatric PICS), Impact of Event Scale-Revised (≥ 25 defined psychiatric PICS), EuroQoL 5-dimension 5-level, Clinical Frailty Scale hand-grip strength, and Medical Research Council. Each disability, employment, destination, and survival, were followed over the first year of hospital discharge. In total, 220 ICU patients were included (median age: 72.5 yr, 129 males (59%), 166 septic shocks (75%), and median Sequential Organ Failure Assessment Score: 8). Four phenotypes were identified: group 1 (n = 62) with no PICS, group 2 (n = 55) with mild PICS (physical and cognitive), group 3 (n = 53) with moderate PICS (all domains), and group 4 (n = 50) with severe PICS (all domains). Functional decline and recovery significantly varied among the phenotypes. Physical and cognitive PICS in group 2 improved by the 3-month follow-up, whereas the disabilities in groups 3 and 4 remained over the year. Psychiatric PICS in groups 3 and 4 ameliorated, whereas depression symptoms in group 4 were still evident at the 12-month follow-up. All groups showed persistent moderate to severe reduced QoL and low employment (0-50%). The survival in group 4 continuously decreased. CONCLUSIONS: Four clinical phenotypes of ICU sepsis survivors might contribute to a deeper understanding of post-sepsis trajectories and an individualized treatment approach.