A variety of different symbiotic microbial communities are harbored on the surface of seaweeds, the interactions of which depend upon nutritional exchanges between the microbes and the hosts. Metabolomic profiling is able to provide a comprehensive and unbiased snapshot of the metabolites associated with seaweed-microbe interactions. In this study, the relationships between phycosphere bacteria and the red alga Pyropia haitanensis were investigated on a metabolomic basis using gas chromatography-mass spectrometry, and the pathways of the interactions between the seaweed and its associated phycospheric microbes were revealed. Bacillus sp. WPySW2, one bacterial species isolated from the phycosphere of Pyropia species, had a significant influence on the metabolomic profile of the algae. Some of the intracel-lular metabolites such as phenylalanine, leucine, isoleucine, valine, proline, tyrosine, threonine, octadecanoic acid, hexadecanoic acid, and citric acid were downregulated in the thalli of P. haitanensis when it was co-cultured with Bacillus sp. WPySW2, while several special metabolites including melibiose, serine, glycerol-3-phosphate, galactosylglycerol, and alanine were upregulated. The results demonstrated that P. haitanensis grew better when it was co-cultured with Bacillus sp. WPySW2 at 20 °C. In conclusion, several main intracellular metabolites were downregulated and upregulat-ed, which might have facilitated bacterial colonization.