AbstractHuman adenoviruses (HAdVs) of the F species are commonly responsible for acute gastroenteritis. A few cases of systemic infections have been described in adults or children who have received a hematopoietic stem cell transplant (HSCT), but with no report of liver cytolysis. Since January 2022, several countries have reported an increase in cases of acute hepatitis of unknown cause in children. Adenovirus species F type 41 (HAdV‐F41) infection was predominantly identified. The objective of this study is to describe HAdV‐F41 infections diagnosed since January 2022 in adult HSCT recipients in two French hospitals. All four patients had diarrhea and liver cytolysis at the time of diagnosis of infection. HAdV viremia was observed in three patients (#1, #3, and #4), but no disseminated disease was reported. HAdV whole genome sequencing and metagenomics characterization were performed on stool and blood samples. The complete HAdV‐F41 genome sequence was obtained for three patients and phylogenetic analysis showed that the strains consisted of similar lineage (2b). We did not identify any new HAdV‐F41 strains. Metagenomics analysis found adeno‐associated virus 2 and torque‐teno virus infection in patient #1 and Epstein–Barr virus in patient #4. This is the first case series reporting liver cytolysis during HAdV‐F41 infection in adult HSCT patients.