Cephalopod molluscs are a large and complex taxonomic group, acting as keystone species in multiple global food webs. Their value in fisheries and aquaculture continues to grow as fin-fish stocks decline, and there is growing interest in expanding aquaculture to new species of cephalopods. While welfare concerns for cephalopods are now at the forefront in the realms of scientific research and in educational settings, welfare of fished or aquacultured cephalopods remains largely overlooked. Here, welfare risks to fished and aquacultured cephalopods are considered with a primary focus on pain and suffering at points of human contact, including slaughter. Critical gaps in knowledge are highlighted, which, if addressed, could lead to measurable improvements in welfare, and suggest a set of key welfare indicators that can be used by veterinary and other professionals charged with assessing well-being and health status of aquacultured cephalopods.