Caulerpa lentillifera is one of the most important economic green macroalgae in the world. Increasing demand for consumption has led to the commercial cultivation of C. lentillifera in Japan and Vietnam in recent decades. Concomitant with the increase of C. lentillifera cultivation is a rise in disease. Both causal and environmental factors responsible for the disease remain unclear. Hence, to determine the identity of the causal organism on the C. lentillifera, the prokaryotic and eukaryotic microorganism community structures and diversities of healthy and diseased C. lentillifera were explored using 16S rDNA, 18S rDNA, and ITS high-throughput sequencing.