The bacterial communities of the sea grape Caulerpa lentillifera were studied during a disease outbreak in Vietnam. The Rhodobacteraceae and Rhodovulum dominated the composition of healthy C. lentillifera. Clear differences between healthy and diseased cases were observed at order, genus and Operational Taxonomic Unit (OTU) level. Bacterial diversity was lower in healthy C. lentillifera, probably because of antimicrobial compounds from the macroalgae and/or from Clostridium, Cutibacterium or Micrococcus bacteria. The likely beneficial role of Bradyrhizobium, Paracoccus and Brevundimonas strains on nutrient cycling and phytohormone production was discussed. The white coloration of diseased C. lentillifera may not only be associated with pathogens but also with an oxidative response. Aquibacter, Winogradskyella and other OTUs of the family Flavobacteriaceae were hypothesized as detrimental bacteria, this family comprises some well-known seaweed pathogens. Moreover, Thalassobius OTU 2935 and 1635 may represent detrimental Rhodobacteraceae. Phycisphaera together with other Planctomycetes and Woeseia were probably saprophytes of C. lentillifera. This study offers pioneering insights on the co-occurrence of C. lentillifera-attached bacteria, potential detrimental or beneficial microbes, and a baseline for understanding the C. lentillifera holobiont. Further metagenomic and biotechnological approaches are needed to confirm functions of some microbes on this macroalgae to enhance food security in the tropics.