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<i>Burkholderia pseudomallei</i>, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Currently, no experimental studies have investigated the effects of binge alcohol on the adaptive immune system during an active infection. In this study, we used <i>B. thailandensis</i> and <i>B. vietnamiensis,</i> to investigate the impact of a single binge alcohol episode on the humoral response during infection. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking (4.4 g/kg) or PBS intraperitoneally 30 min before intranasal infection. Mice infected with <i>B. thailandensis</i> had a 100% survival rate, while those infected with <i>B. vietnamiensis</i> had a 33% survivability rate when a binge alcohol dose was administered. <i>B. thailandensis</i> was detected in blood of mice administered alcohol at only 7 days post infection (PI), while those infected with <i>B. vietnamiensis</i> and receiving alcohol were found throughout the 28-day infection as well as in tissues at day 28 PI. Binge alcohol elevated IgM and delayed IgG specific to the whole cell lysate (WCL) of <i>B. vietnamiensis</i> but not <i>B. thailandensis</i> infections. Differences in immunogenicity of <i>B. pseudomallei</i> near-neighbors provide a framework for novel insights into the effects of binge alcohol&#8217;s suppression of the humoral immune response that can cause opportunistic infections in otherwise healthy hosts.