Pyogenic liver abscess (PLA) is a potentially life-threatening disease. Early diagnosis and appropriate treatment are crucial to ensure high-quality healthcare for patients with PLA. However, this is complicated by their non-specific clinical symptoms. In addition, the etiologic organisms responsible for PLA are frequently culture-negative, thus complicating clinical decision-making. Here, we report a case of PLA caused by Streptococcus intermedius, as identified via DNA metagenomic sequencing of plasma.