Palliative sedation for existential suffering (PS-ES) is a controversial clinical intervention. Empirical studies about physicians' perceptions do not converge in a clear position and current clinical practice guidelines do not agree either regarding this kind of intervention.To gain deeper insight into physicians' perceptions of PS-ES, the factors influencing it, the conditions for implementing it and the alternatives to it.Systematic review of qualitative, quantitative and mixed-methods studies following the and protocols; quality appraisal and thematic synthesis methodology.Seven electronic databases (PubMed, CINAHL, Embase, Scopus, Web of Science, PsycINFO, PsycARTICLES) were exhaustively searched from inception through March 2019. Two reviewers screened paper titles, abstracts and full texts. We included only peer-reviewed journal articles published in English, French, German, Dutch, Spanish, Italian or Portuguese that focused on physicians' perceptions of PS-ES.The search yielded 17 publications published between 2002 and 2017. Physicians do not hold clear views or agree if and when PS-ES is appropriate. Case-related and individual-related factors that influenced physicians' perceptions were identified. There is still no consensus regarding criteria to distinguish between necessary and sufficient conditions for invoking PS-ES. Some alternatives to PS-ES were identified.To date, there is still no consensus on physicians' perceptions of PS-ES. Further research is necessary to understand factors that influence physicians' perceptions and philosophical-ethical presuppositions underlying this perceptions.