Abstract: Kelps are pivotal to temperate coastal ecosystems, providing essential habitat and nutrients for diverse marine life, and significantly enhancing local biodiversity. The impacts of elevated CO₂ levels on kelps may induce far-reaching effects throughout the marine food web, with potential consequences for biodiversity and ecosystem functions. This study considers the kelp Macrocystis pyrifera and its symbiotic microorganisms as a holistic functional unit (holobiont) to examine their collective response to heightened CO₂ levels. Over a 4 month cultivation from the fertilization of M. pyrifera gametes to the development of juvenile sporophytes, our findings reveal that elevated CO₂ levels influence the structure of the M. pyrifera symbiotic microbiome, alter metabolic profiles, and reshape microbe-metabolite interactions using 16S rRNA amplicon sequencing and liquid chromatography coupled to mass spectrometry analysis. Notably, Dinoroseobacter, Sulfitobacter, Methylotenera, Hyphomonas, Milano-WF1B-44 and Methylophaga were selected as microbiome biomarkers, which showed significant increases in comparative abundance with elevated CO₂ levels. Stress-response molecules including fatty-acid metabolites, oxylipins, and hormone-like compounds such as methyl jasmonate and prostaglandin F2a emerged as critical metabolomic indicators. We propose that elevated CO₂ puts certain stress on the M. pyrifera holobiont, prompting the release of these stress-response molecules. Moreover, these molecules may aid the kelp's adaptation by modulating the microbial community structure, particularly influencing potential pathogenic bacteria, to cope with environmental change. These results will enrich the baseline data related to the chemical interactions between the microbiota and M. pyrifera and provide clues for predicting the resilience of kelps to future climate change.