Disease outbreaks in oyster hatcheries can decimate the stock, delay production, and cause supply chain shortages for the expanding oyster aquaculture industry. The daily addition of the probiotic bacterium Phaeobacter inhibens S4 (S4) to hatchery tanks has been demonstrated to protect eastern oyster, Crassostrea virginica, larvae against bacterial pathogens such as Vibrio coralliilyticus RE22 (RE22). Mechanisms of action of S4 against RE22 pathogenicity in oysters are complex, including antibiotic production, formation of thick biofilms, decrease in virulence through quorum quenching, and host immunomodulation. To better understand the ways in which S4 helps protect oyster larvae against vibriosis, a competition assay was performed between S4 and RE22, following which RNA was sequenced and differential gene analysis performed. In addition to downregulation of several virulence factors, analysis of the transcriptomic data uncovered decreased expression of several flagellar protein genes, including flagellin, flgA, flgE, fliD, and fliL, in RE22 co-cultured with S4. Reduced RE22 motility in the presence of tropodithietic acid (TDA), an antibiotic produced by S4, has been previously reported. However, this transcriptome analysis indicated that this effect of S4 on RE22 motility may also be due to downregulation of disulfide bond family protein genes dsbA and dsbD. Mutations or deletions of dsbA have been linked to decreased virulence and motility in gram-negative bacteria, including other Vibrio species. By now including downregulation of flagellar function, this study further highlights the complex ways in which S4 may be able to reduce RE22’s devastating effect on oyster larvae, protecting this vital aquaculture commodity.