The global spread of highly pathogenic avian influenza (H5N1) clade 2.3.4.4b has evolved into a multispecies panzootic that disrupts conventional boundaries between human, animal and environmental health systems. Using Brazil’s response as an illustrative case, this article argues that prevailing containment strategies—particularly mass culling—remain ethically insufficient and practically misaligned with the ecological complexity of H5N1 transmission. To clarify the normative foundations of an alternative approach, we introduce a theoretical framework grounded in zoonoethics and global ecological bioethics, emphasizing multispecies justice, relational vulnerability, intercultural and community engagement and co-responsibility. We then apply this framework to evaluate the limitations of reactive biosecurity paradigms and to outline multispecies-sensitive One Health governance guidelines. The analysis demonstrates that effective and legitimate panzootic response requires moving beyond biomedical and anthropocentric models toward anticipatory, inclusive and ethically grounded governance capable of addressing structural drivers such as biodiversity loss, land-use change and the erosion of Indigenous territorial protections. We conclude by discussing how the H5N1 panzootic represents a ‘perfect storm’ that demands not only improved preparedness, but a reconceptualization of One Health as an ethical and political project of multispecies cohabitation in an era of planetary instability.