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Background Anemonefish association with sea anemones is a prime example of mutualistic symbiosis. These fish live inside the sea anemone, benefitting from the protection of its toxic nematocysts, and in return, protect the anemone from its own predators. How anemonefish manage to avoid their host toxic stings remains unclear. One hypothesis suggests that low levels of sialic acids in anemonefish mucus prevent nematocyst discharge. Results This study verified four predictions: (i) anemonefish mucus has lower sialic acid levels than non-symbiotic damselfish; (ii) this reduction is specific to mucus; (iii) during development, sialic acid levels inversely correlate with protection; (iv) sea anemone mucus has minimal sialic acids. Conclusions We conclude that anemonefish regulates the level of sialic acids in their mucus to avoid nematocyst discharge. We also highlight several genes implicated in sialic acid removal that could explain the protection mechanisms in place. This mechanism, potentially used by Dascyllus trimaculatus juveniles, suggests a convergent strategy for mutualistic associations with sea anemones.