Diagnosis of Klebsiella pneumoniae (Kp) pyogenic liver abscesses is usually achieved by imaging and isolation of the bacterium. However, when blood and other cultures were negative, laboratory diagnosis of Kp liver abscess may be challenging. Herein we report two patients with culture-negative Kp liver abscess with atypical presentations diagnosed by metagenomic next-generation sequencing (mNGS). For the first non-diabetic patient, computed tomography examination of the abdomen showed multiple round low-density foci with untidy margin in the liver, which mimicked hydatid cysts; while the second patient presented with acute cholecystitis/cholangitis. mNGS analysis of the blood sample from the first patient revealed 144 sequence reads of Kp; and that of the second revealed 153 sequence reads of Kp as well as other latent or non-pathogenic microorganisms. Both patients responded promptly to antibiotics treatment. mNGS is a useful tool for laboratory diagnosis of culture-negative Kp liver abscess.