South America has extraordinary biodiversity, with an immense variety of invertebrate species playing a critical role in ecosystems. Molluscs and crustaceans support fisheries and aquaculture worldwide, but their populations are increasingly threatened by pathogens. Understanding host-parasite interactions is essential for managing disease outbreaks and ensuring the sustainability of both natural ecosystems and aquaculture systems. Bivalves, gastropods and crustaceans are hosts to numerous lineages of parasites, highlighting the interactions that shape ecological dynamics and influence both conservation efforts and disease management strategies. This special issue presents a range of studies pertaining to invertebrate pathology from the South American region, including viral, protozoan and metazoan diseases across a wide range of host species. It also explores advances in pathology, immunology, genomics, phylogenetic and ecological associations.