Killer whales (Orcinus orca), sperm whales (Physeter macrocephalus) and fur seals (Arctocephalus sp.) interactions with longlines fishing operations were reported by observers onboard of fishing vessels, catching Patagonian tooshfish in the Crozet and Kerguelen Exclusive Economic Zones, between 2003 and 2005. In Crozet waters, 71% of the 1308 longlines presented marine mammals interactions with killer whales and/or sperm whales. On the other hand, fur seals and/or sperm whales were present in 54% of the 6262 longlines monitored in the Kerguelen waters. Interactions occurred over the whole fishing areas even if contrasted situations regarding the marine mammal species are observed between localities. Depredation effect was assessed by comparing CPUEs of the longlines, in absence/presence of any marine mammals species alone or in association. In Crozet waters, the CPUE was found to be reduced by both killer whales and sperm whales presence by themselves or associated. An important photo-identification effort mainly dedicated to killer whales allowed to identify 103 individuals. However, few individuals are responsible for most of the interactions with the fishery. In Kerguelen waters CPUE tended to decrease in presence of sperm whales alones or in association with fur seals.