The aim of this study was to synthesize quantitative research that identified ranking lists of the most severe stressors of patients in the intensive care unit, as perceived by patients, relatives, and health care professionals (HCP). We conducted a systematic literature search in PubMed, MEDLINE, EMBASE, PsycInfo, CINAHL, and Cochrane Library from 1989 to 15 May 2020. Data were analyzed with descriptive and semi-quantitative methods to yield summarizing ranking lists of the most severe stressors. We synthesized the results of 42 prospective cross-sectional observational studies from different international regions. All investigations had assessed patient ratings. Thirteen studies also measured HCP ratings, and four studies included ratings of relatives. Data indicated that patients rate the severity of stressors lower than HCPs and relatives do. Out of all ranking lists, we extracted 137 stressor items that were most frequently ranked among the most severe stressors. After allocation to four domains, a group of clinical ICU experts sorted these stressors with good to excellent agreement according to their stress levels. Our results may contribute to improve HCPs’ and relatives’ understanding of patients’ perceptions of stressors in the ICU. The synthesized stressor rankings can be used for the development of new assessment instruments of stressors.