Background: Better understanding of patients’ and their family members’ experiences of delirium and related distress during critical care is required to inform the development of targeted nonpharmacologic interventions. Objective: To examine and synthesize qualitative data on patients’ and their family members’ delirium experiences and relieving factors in the Intensive Care Unit (ICU). Design: We conducted a systematic review and qualitative meta-synthesis. Eligible studies contained adult patient or family quotes about delirium during critical care, published in English in a peer-reviewed journal since 1980. Data sources included PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane and Clinicaltrials.gov . Methods: Systematic searches yielded 3238 identified articles, of which 14 reporting 13 studies were included. Two reviewers independently extracted data into a Microsoft Excel spreadsheet. Qualitative meta-synthesis was performed through line-by-line coding of relevant quotes, organisation of codes into descriptive themes, and development of analytical themes. Five patients/family members with experience of ICU delirium contributed to the thematic analysis. Results: Qualitative meta-synthesis resulted in four major themes and two sub-themes. Key new patient and family-centric insights regarding delirium-related distress in the ICU included articulation of the distinct emotions experienced during and after delirium (for patients, predominantly fear, anger and shame); its ‘whole-person’ nature; and the value that patients and family members placed on clinicians’ compassion, communication, and connectedness. Conclusions: Distinct difficult emotions and other forms of distress are experienced by patients and families during ICU delirium, during which patients and family members highly value human kindness and empathy. Future studies should further explore and address the many facets of delirium-related distress during critical care using these insights and include patient-reported measures of the predominant difficult emotions.