BackgroundPsychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts. AimsThis study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022. MethodsWe analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence. ResultsWe identified 28 cases where psychedelics were implicated (75 %, N = 21) or potentially implicated (25 %, N = 7) in the death; 19 of these involving psychedelic tryptamines (LSD 39 %, N = 11; Psilocybin 21 %, N = 6; DMT 7 %, N = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, N = 5). Most deaths were deemed accidental by the coroner (86 %, N = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, N = 19); and most of the deceased were under 30 years of age (82 %, N = 23). Thematic framework analysis identified nine themes in the deaths across three categories. ‘Polysubstance use’ was the most common theme (82 % of cases, N = 23/28), followed by a suboptimal ‘physical environment’ (70 % of cases where this information was available, N = 14/20). ConclusionsThe profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.