We compared three primer sets targeting different hypervariable regions of the 16S rRNA gene, V1V2, V3V4, and V4V5, which have been commonly used in cnidarian literature. Our model is the jellyfish, Rhopilema nomadica, which forms massive blooms in the Eastern Mediterranean with significant ecological and economic impacts. The goal was to find which one of these primers is best-suited for studying the jellyfish microbial community.