At subduction zones, fluid circulation and elevated pore pressure are key factors controlling the seismogenic behavior along the plate interface by reducing absolute fault strength, increasing the time return of high magnitude co-seismic rupture and favoring aseismic slip. The Lesser Antilles is an endmember subduction zone where the slow subduction of numerous trans-oceanic fracture zones and patches of pervasively fractured, hydrated and serpentinized exhumed mantle rocks increase the water input. Heat-flow variations measured in the trench and the forearc during the Antithesis 1 cruise reveal heat advection by fluid circulation and shed a new light onto the thermal control of seismicity location in the subduction zone. In the Northern Lesser Antilles, heat-flow anomalies, negative in the trench and positive in the forearc, reveal a ventilated fluid circulation with downward percolation of cold fluids at the sediment-starved, pervasively fractured trench and upward discharge of warm fluids through the Tintamarre Fault Zone in the forearc. In contrast, in the Central Lesser Antilles, a positive heat-flow anomaly at the trench and the accretionary wedge is typical of an insulated fluid circulation where warm fluids invade the plate interface flowing updip from the subduction depths up to the trench. The investigated margin segments correspond with a very low number of interplate thrust earthquakes, illustrating the frequent statement that fluids in subduction zones tend to reduce the interplate coupling, favor slow to aseismic slip behavior, and increase the time return of large seismic events. Moreover, the location of intraslab, and supraslab earthquakes at depth beneath the Central Lesser Antilles suggest a close relation to temperature-related dehydration reactions.