Depredation is defined as the damage or removal of fish from fishing gear by predators, and is an issue leading to negative impacts on animals involved in depredation and fisheries. Depredation on pelagic longliners targeting swordfish (Xiphias gladius) and tuna (Tuna spp) involves short-finned pilot whales (Globicephala macrorhynchus), false killer whales (Pseudorca crassidens) and some pelagic sharks. In the Seychelles archipelago, a database was built to assess its extent on the pelagic longline fishery and to identify fishing practices likely to influence depredation. Data were collected from pre-existing databases, fishermen logbooks and satellite-based Vessel Monitoring System information, and covered the 2002-2006 period, representing a total of 705 fishing operations. The number of sets impacted by shark depredation was significantly greater than the number of sets involving toothed whale depredation. Nevertheless, when depredation occurred, the proportion of fish damaged by toothed whales was significantly greater. Depredation occurrence was analyzed by using logistic regression. Toothed whale depredation occurrence was positively related to the abundance of target fish and the fishing area (being more frequent in the south-west of the archipelago). Shark depredation was more frequent in the north-west of the archipelago. Depredation rate was analyzed by implanting Generalized Additive Models. Toothed whale depredation rate depended on the fishing area. Shark depredation rate was negatively related to the longline length and the latitude. Both depredation types occurred in areas of high CPUE (Catch Per Unit Effort), suggesting the co-occurrence of sharks and toothed whales in areas of high concentration of pelagic fish. Otherwise, toothed whales damaged significantly more swordfish than tuna, whereas sharks equally damaged both species. The global depredation rate reached 19.3% (10.7% were due to toothed whales and 8.6% were due to sharks). No obvious answers can be given by modifying fishing practices and other solutions have to be investigated to reduce depredation impacts.