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Corals are important models for understanding invertebrate host–microbe interactions; however, to fully discern mechanisms involved in these relationships, experimental approaches for manipulating coral–bacteria associations are needed. Coral‐associated bacteria affect holobiont health via nutrient cycling, metabolic exchanges and pathogen exclusion, yet it is not fully understood how bacterial community shifts affect holobiont health and physiology. In this study, a combination of antibiotics (ampicillin, streptomycin and ciprofloxacin) was used to disrupt the bacterial communities of 14 colonies of the reef framework‐building corals Pocillopora meandrina and P. verrucosa, originally collected from Panama and hosting diverse algal symbionts (family Symbiodiniaceae). Symbiodiniaceae photochemical efficiencies and holobiont oxygen consumption (as proxies for coral health) were measured throughout a 5‐day exposure. Antibiotics altered bacterial community composition and reduced alpha and beta diversity, however, several bacteria persisted, leading to the hypothesis that these bacteria are either antibiotics resistant or occupy internal niches that are shielded from antibiotics. While antibiotics did not affect Symbiodiniaceae photochemical efficiency, antibiotics‐treated corals had lower oxygen consumption rates. RNAseq revealed that antibiotics increased expression of Pocillopora immunity and stress response genes at the expense of cellular maintenance and metabolism functions. Together, these results reveal that antibiotic disruption of corals' native bacteria negatively impacts holobiont health by decreasing oxygen consumption and activating host immunity without directly impairing Symbiodiniaceae photosynthesis, underscoring the critical role of coral‐associated bacteria in holobiont health. They also provide a baseline for future experiments that manipulate Pocillopora corals' symbioses by first reducing the diversity and complexity of coral‐associated bacteria. [ABSTRACT FROM AUTHOR]