Interactions between killer whales (Orcinus orca), sperm whales (Physeter macrocephalus), fur seals (Arctocephalus spp.) and longline fishing operations were reported by observers on board fishing vessels targeting Patagonian toothfish (Dissostichus eleginoides) in the Crozet and Kerguelen Islands Exclusive Economic Zones (EEZs) between 2003 and 2005. In the Crozet EEZ, the reported interactions involved killer whales and sperm whales. These two species, alone or in co-occurrence with each other, were observed in 71% of the 1 308 longlines set. In the Kerguelen EEZ, the reported interactions involved sperm whales and fur seals. These two species, alone or in co-occurrence with each other, were observed in 54% of the 6 262 longlines monitored. Interactions were observed in all fishing areas. The effect of depredation was assessed by comparing catch-per-unit-effort (CPUE) (fish/weight/hook) of each longline set in the absence/presence of marine mammal species alone or in co-occurrence. In the Crozet EEZ, CPUE was found to be reduced by 22.5% in the presence of killer whales, 12.1% by sperm whales, and 42.5% when both species were present together. An extensive photo-identifi cation effort, primarily focussing on killer whales, allowed a total of 103 individual whales to be identifi ed. The analysis of photoidentification indicated that a small number of individual killer whales were responsible for most of the interactions with the fishery. In the Kerguelen EEZ only sperm whales, alone or in co-occurrence with fur seals, were found to impact negatively on CPUE.