The bacterial communities of
Caulerpa lentillifera
were studied during an outbreak of an unknown disease in a sea grape farm from Vietnam. Clear differences between healthy and diseased cases were observed at the order, genus, and Operational Taxonomic Unit (OTU) level. A richer diversity was detected in the diseased thalli of
C. lentillifera
, as well as the dominance of the orders Flavobacteriales (phylum Bacteroidetes) and Phycisphaerales (Planctomycetes).
Aquibacter, Winogradskyella
, and other OTUs of the family Flavobacteriaceae were hypothesized as detrimental bacteria, this family comprises some well‐known seaweed pathogens.
Phycisphaera
together with other Planctomycetes and
Woeseia
were probably saprophytes of
C. lentillifera
. The Rhodobacteraceae and
Rhodovulum
dominated the bacterial community composition of healthy
C. lentillifera
. The likely beneficial role of
Bradyrhizobium, Paracoccus
, and
Brevundimonas
strains on nutrient cycling and phytohormone production was discussed. The bleaching of diseased
C. lentillifera
might not only be associated with pathogens but also with an oxidative response. 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 applied and basic research is urgently needed on
C. lentillifera
microbiome, shotgun metagenomic, metatranscriptomic, and metabolomic studies as well as bioactivity assays are recommended.