Résumé: Depredation in marine ecosystems is defined as the damage or removal of fish or bait from fishing gear by predators. Depredation raises concerns about the conservation of species involved, fisheries yield and profitability, and reference points based on stock assessment of depredated species. Therefore, the development of accurate indicators to assess the impact of depredation is needed. Both the Reunion Island and the Seychelles archipelago pelagic longline fisheries targeting swordfish (Xiphias gladius) and tuna (Thunnus spp.) are affected by depredation from toothed whales and pelagic sharks. In this study, we used fishery data collected between 2004 and 2015 to propose depredation indicators and to assess depredation levels in both fisheries. For both fisheries, the interaction rate (depredation occurrence) was significantly higher for shark compared to toothed whale depredation. However, when depredation occurred, toothed whale depredation impact was significantly higher than shark depredation impact, with higher depredation per unit effort (number of fish depredated per 1000 hooks) and damage rate (proportion of fish depredated per depredated set). The gross depredation rate in the Seychelles was 18.3%. A slight increase of the gross depredation rate was observed for the Reunion Island longline fleet from 2011 (4.1% in 2007–2010 and 4.4% in 2011–2015). Economic losses due to depredation were estimated by using these indicators and published official statistics. A loss of 0.09 EUR/hook due to depredation was estimated for the Reunion Island longline fleet, and 0.86 EUR/hook for the Seychelles. These results suggest a southward decreasing toothed whale and shark depredation gradient in the southwest Indian Ocean. Seychelles depredation levels are among the highest observed in the world revealing this area as a “hotspot” of interaction between pelagic longline fisheries and toothed whales. This study also highlights the need for a set of depredation indicators to allow for a global comparison of depredation rates among various fishing grounds worldwide.