A number of cephalopod species present substantial ecological and economical importance; however, data on the physiology of stress and on regulatory processes linking stress to immune defence against pathogens remain extremely scarce in these organisms. The present study examined the influence of a 5 min air exposure, a common perturbation associated with handling in aquaculture settings and fisheries, on neuroendocrine and immune parameters in the octopus Eledone cirrhosa. Measurements of circulating concentrations of noradrenaline and dopamine, two hormones that are released in the haemolymph during stress in bivalves and gastropods, showed that the 5 min air exposure represents a real stress to octopus. Indeed, blood levels of both hormones increased by about 2–2.5-fold in stressed animals. Concomitantly, a significant decrease in the number of circulating haemocytes was observed, whereas haemocyte phagocytotic activity and superoxide anion production increased transiently between 5 and 60 min after the beginning of the stress. These results provide a first insight into the effects of stress on catecholamine levels and immune functions in cephalopods and suggest that stress and immunity may be associated in these organisms.