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French Guiana region is one of the most productive in the world and hosts a wide variety of marine vertebrates. In the same time, anthropogenic activities are a growing concern in French Guiana, both in coastal and offshore areas. However, few studies are published on marine mammals, seabirds and potential interactions. Twenty-three marine mammal species are known to occur in the Exclusive Economic Zone (EEZ) and important seabird breeding sites are located in the area. Most of the existing literature relates to breeding birds and coastal cetaceans, but the continental slope appears to be an essential habitat for marine mammals and seabirds. Between October 22 and November 23, 2017, an oceanographic survey was conducted on the Guiana slope to study the quality of sediments and water. Three marine fauna observers (MFOs) were onboard to record sightings of marine mammals and seabirds opportunistically. During 462 h of visual effort in good sighting conditions, 313 sightings (824 individuals) were recorded: 61 marine mammals (501 individuals) and 252 seabirds (323 individuals). Seven seabird families were observed: Laridae (42%), Fregatidae (26%), Procellariidae (12%), Stercorariidae (10%), Hydrobatidae (4%), Sulidae (2%) and Phaethontidae (1%). 3% concerned wader species. The most frequently observed seabird species was the magnificent frigatebird ( Fregata magnificens ), as well as the common tern ( Sterna hirundo ), Cory’s shearwater ( Calonectris diomedea ) and the pomarine jaeger ( Stercorarius pomarinus ). Many Delphinidae species were observed ( Stenella longirostris , Stenella attenuata , Stenella frontalis , Delphinus delphis , Tursiops truncatus ) in addition to sperm whales ( Physeter macrocephalus ) and humpback whales ( Megaptera novaeangliae ). Only a few sightings of humpback whales have been previously recorded in this area. Sighted individuals were mainly mother-calf pairs suggesting that the area may be an extended part of a calving ground for humpback whales.