Abstract Mesoscale physical features as fronts and eddies appear to play a key role in the dynamics of marine communities. In the Indian Ocean, the Mozambique Channel (MC) is a natural laboratory to investigate mesoscale eddies (100–300 km in diameter); indeed, four to seven eddies per year are know to transit through the Channel, from North to South. We studied the structuring role of the mesoscale eddies on spatial dynamics and foraging strategy of top predators using seabirds and tuna as examples. Emphasis was on the central part of the MC (16–24°S) where eddy activity is most developed. We integrated three main categories of information: (i) satellite altimetry for sea-level anomaly (SLA) and geostrophic current, remotely-sensed surface temperature (SST) and SeaWiFS data for chlorophyll concentration (CC); (ii) individual tracking of Great Frigatebirds ( Fregata minor) to characterize foraging areas; and (iii) detailed catch statistics from purse-seine fisheries to describe distribution of tuna schools. Generalized Additive Models were applied to quantify the relative influence of mesoscale descriptors, SST and CC on foraging behaviour of Great Frigatebirds and location of purse-seine sets. Our results show that seabirds are more closely tied to mesoscale eddies compared to tuna. We underline the role of eddy boundaries on the response of frigatebirds and tuna. Good foraging conditions are promoted along the edge of eddies as a result of the interplay of the maturation process from cyclonic eddies and the concentration process by eddy interactions. A decrease in the number or intensity of eddies in the MC, as observed during strong El Niño events, could potentially affect the eddy-related ecosystem with putative negative repercussions on central-place foragers such as Great Frigatebirds. We discuss the importance of a better understanding of the “eddy system”, in marine conservation and tuna fisheries management in the Mozambique Channel.