Giant sea anemones and anemonefish form a quintessential reef mutualism, where anemonefish provide nutrients and maintenance in exchange for habitat and predator protection. Due to climate change and rising seawater temperatures, giant sea anemone bleaching is increasing in frequency globally. While this significantly impacts the anemones’ metabolic status, immune function, and causes oxidative stress, little is known about how host bleaching affects the dynamics of this symbiotic relationship and the physiological responses of the resident anemonefish. To address this, we explored the impact of host bleaching on the false clownfish Amphiprion ocellaris at the tissue-level through transcriptomic analysis of the brain and liver. Contrasting two host anemone species, we focused on two timepoints - pre-bleaching and during bleaching - tracking the acute impacts on anemonefish of a natural heatwave that induced bleaching in outdoor experimental flow-through tanks in Okinawa. Through this study, we showed that host anemone bleaching impacts the transcriptomic landscape and physiological state of anemonefish. Among thousands of differentially expressed genes, we identified shifts in energy production, fatty acid synthesis, stress response, and hormonal regulation in the brain and liver, with host species-specific effects on strategies employed to survive. This reinforces our understanding of the invisible impacts of anemone bleaching on the anemonefish, contributing to the elucidation of the tenets of their symbiosis and its future under climate change.