OBJECTIVE: Targeted temperature management (TTM), through its physiological effects on intracranial pressure, may impede the progression to brain death (BD) in severe anoxic brain injury post-cardiac arrest (CA). We examined the potential association between the use of TTM and the occurrence of BD after CA. DESIGN: Monocentric, retrospective study. SETTING: Intensive care unit, Versailles Hospital, France. PARTICIPANTS: Comatose survivors of CA who died from BD or postanoxic encephalopathy (PAE) after 24 hours. MAIN OUTCOME MEASURES: PAE deaths corresponded to withdrawal of life-sustaining therapy (WLST) due to irreversible postanoxic coma or vegetative state according to prognostication guidelines. BD corresponded to the cessation of cerebral vascularisation secondary to intracranial hypertension. The diagnosis of BD was definite by clinical diagnosis of deep coma according to the Glasgow Coma Scale 3, loss of all brainstem reflexes and the demonstration of apnoea during a hypercapnia test. A cerebral omputed tomography (CT) scan or two isoelectric and unreactive electroencephalograms were used to confirm BD. To identify the independent association between TTM and BD, we conducted a multivariable logistic regression analysis. RESULTS: Out of 256 patients included between 2005 and 2021, 54.3% received TTM for at least 24 hours, and 56 patients (21.9%) died from BD. In the multivariable analysis, TTM for 24 hours or more was not associated with a decrease in BD (Odds Ratio 1.08, 95% CI 0.51 to 2.32). Factors associated with BD included a total duration of no-flow plus low-flow exceeding 30 min, CA due to neurological causes or hanging and a high arterial partial pressure of carbon dioxide between days 1 and 2 after admission. CONCLUSIONS: This exploratory analysis of post-CA patients with severe anoxic brain injury did not find an association between TTM ≥24 hours and a reduction in BD. Further studies are needed to identify specific subgroups of post-CA patients for whom TTM may be especially futile or even harmful.