In recent decades, mass mortality events (MMEs) among aquatic mammals have been caused by morbillivirus or avian influenza virus (AIV) infections. Thus far, AIV infections have been predominantly associated with direct or indirect contact with infected birds, while mammal-to-mammal AIV transmission has not been formally proven in most cases. However, amino acid changes in the HA or PB2 RNA segments previously identified as ´mammalian-adapting mutations´ have been documented during AIV epizootics in aquatic mammals. Such mutations are known to increase infectivity and/or virulence of AIV in mammalian species, including humans. Epizootics caused by low-pathogenic AIV (LPAIV) are typically self-limiting respiratory disease outbreaks. In contrast, the ongoing panzootic caused by highly pathogenic AIV (HPAIV) subtype A(H5N1) clade 2.3.4.4b is associated with severe neurological disease and mortality in infected pinniped and cetacean species. The available serological data suggest that enzootic circulation of AIV in aquatic mammals is limited. LPAIV-specific antibodies have been detected in pinniped species only during documented flu outbreaks and have then decreased to undetectable levels, while no AIV-specific antibodies have been detected following recent HPAIV A(H5N1) infections. Since direct interventions in wild pinnipeds are limited, AIV surveillance and investigations into the genetic and phenotypic characteristics of AIVs associated with MMEs in aquatic mammals will be essential to better understand the risk that these viruses pose to often endangered animal populations, as well as to public health.