Observer data collected on longliners between 2003 and 2009 were analysed to look at the levels of depredation caused by killer whales (Orcinus orca) and sperm whales (Physeter macrocephalus) around South Georgia. Since 2003, cetaceans have been observed on 22% of 14 300 observed lines, with killer whales present on 3.8% and sperm whales on 17.7% of lines. Killer whales appear in pod sizes normally of 4 to 10 animals, and often appear to actively seek out fishing vessels and ‘strip’ the line of a large number of toothfish, usually depressing CPUE by about 50%. Sperm whales occur in smaller pod sizes, normally between 1 and 4 animals, and have a relatively lower impact on catches, depressing CPUE by up to 20%. Sperm whales have been more frequently encountered in recent years, occurring in larger pod sizes, whereas killer whale encounters and pod sizes have remained relatively constant. Most interactions from sperm whales occur during May at the start of the season with the sightings becoming fewer towards the end of the season in August. Killer whale interactions appear to be more consistent with no obvious pattern between months. Both species demonstrate an east to west migration throughout the season that is not related to the pattern of fishing effort. By comparing catch rates with and without the presence of cetaceans, accounting for other determinants of toothfish CPUE through a generalised linear model, it is estimated that the amounts of toothfish removed from longlines by cetaceans have varied between 1% and 8% of the declared catches over the period 2003–2009, with an average of 3.6%.