<p>Coastal hypoxia is an increasing environmental concern affecting marine ecosystems globally, particularly impacting benthic organisms such as bivalves. Although previous studies focused on the physiological responses of bivalves to hypoxic stress, the role of resident bacteria in the host response to hypoxia remains poorly understood. This study investigated changes in the resident bacterial communities in the gills and hepatopancreatic tissues of the ark shell (<i>Anadara kagoshimensis</i>) under hypoxic conditions. Specimens were assigned to three treatment groups: untreated control, hypoxia, and hypoxia with chloramphenicol supplementation (5.0&#xa0;mg/L). After 3&#xa0;days, specimens exposed to hypoxia exhibited black precipitation in the culture water, whereas antibiotic treatment reduced these effects. Amplicon sequencing revealed distinct bacterial communities between the tissues, with Arcobacteraceae and Alkalispirochaetaceae dominating in the gills and Metamycoplasmataceae being predominant in the hepatopancreas. The hepatopancreas displayed greater bacterial community changes than the gills under hypoxic conditions, including an increase in the abundance of Metamycoplasmataceae. The predicted metabolic functions suggested that these bacteria contribute to iron sulfide precipitation through sulfate reduction and iron respiration. The antibiotic-treated group displayed bacterial communities more similar to those of the control group, confirming the effectiveness of chloramphenicol in suppressing bacterial changes under hypoxia. This study provided new insights into tissue-specific bacterial responses to hypoxia in <i>A</i>. <i>kagoshimensis</i> and highlighted the potential role of Metamycoplasmataceae in the bivalve’s response to hypoxic stress.</p>