BackgroundPost-dialysis fever is a common but diagnostically challenging issue in hemodialysis patients, with potential causes including dialysis-related infections, pulmonary infections, and cardiovascular complications.Case presentationWe report a 76-year-old male with end-stage renal disease (ESRD) on maintenance hemodialysis, coronary artery disease, and prior cardiac stent implantation, who presented with recurrent post-dialysis fever. Despite persistently negative conventional cultures, metagenomic next-generation sequencing (NGS) of pre-dialysis blood samples identified Pseudomonas aeruginosa (P. aeruginosa), Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes), Staphylococcus epidermidis (S. epidermidis), and Corynebacterium accolens (C. accolens) and Epstein-Barr virus (EBV), while post-dialysis samples revealed only C. acnes and EBV. Given the temporal association with fever, these two pathogens were considered the primary causative agents. Subsequent transesophageal echocardiography (TEE) confirmed aortic valve vegetations, establishing the diagnosis of infective endocarditis (IE). Following targeted antimicrobial and antiviral adjustments based on NGS findings, the patient exhibited complete resolution of post-dialysis fever and was discharged. However, as the vegetation was not surgically removed, he was hospitalized multiple times over the following five months for recurrent infections and ultimately died of septic shock and multi-organ failure due to carbapenem-resistant Klebsiella pneumoniae.ConclusionsThis case underscores the complementary role of TEE and NGS in diagnosing IE in high-risk patients, enabling the detection of uncommon pathogens and informing targeted therapy to improve clinical outcomes.Clinical trial numberNot applicable.