Baited cameras were deployed over a depth range of 532–5111 m in the Ionian Sea to characterise the large mobile fauna. The planned installation of a neutrino telescope also offers the potential for biological observatories. The current study was intended to aid observatory placement. At increasing depths, sediment was observed to become more uniform and animal burrows and tracks reduced. A total of 10 species of deep-sea fishes were identified from images; four elasmobranchs, which were not recorded deeper than 1841 m, and six teleosts. At depths > 3000 m, including Calypso Deep, the deepest point in the Mediterranean, only one fish species was observed; the Mediterranean grenadier, Coryphaenoides mediterraneus (3400–5111 m), extending this species’ maximum recorded depth to 5111 m. Four species of decapod crustacea could be identified from images. The dressed deep-sea shrimp, Acanthephyra eximia (1346–5111 m) was the only invertebrate recorded at abyssal depths, including the deepest point. A faunal change was detected at ~ 1000 m depth. Incorporating other studies from the Eastern Mediterranean identified additional faunal boundaries at ~ 1500 m and ~ 2500 m. The time from landing the observation equipment to the arrival of the first fish increased exponentially with depth at a slower rate to that observed in the Atlantic Ocean. The estimated density of bait-attending deep-sea fish was, therefore, significantly impoverished compared to the Atlantic Ocean at equivalent depth. Barriers to colonisation, low resource input, and high temperature at depth relative to the Atlantic Ocean are probable causes of the impoverished fauna.