Serpentinization of the mantle wedge immediately above a subducting slab is a key process controlling the strength contrast between the slab and the overriding nominally anhydrous (i.e., olivine-rich) mantle. To assess the influence of serpentinite rheology on the degree of decoupling between the slab and mantle wedge, we conducted axial compression tests on partially foliated antigorite serpentinite using a modified Griggs-type apparatus at confining pressures (Pc) of 1.0–2.5 GPa, temperatures (T) of 300–600 °C, and a strain rate of 1.5 × 10−5 s−1. With increasing temperature, the dependence of maximum differential stress (i.e., strength) on Pc changes from positive to flat, suggesting an increasingly important contribution from plastic deformation. Microstructural observations show that increasing temperature promotes a transition in deformation mechanisms from distributed inter- and intra-granular microcracking to comminution and kinking localized within a through-going shear zone. The ductile-to-brittle transition can be attributed to the operation of thermally activated processes such as dislocation glide and grain boundary sliding in aligned antigorite grains. Comparison with strength data for dunite demonstrates that in the semi-brittle regime, the strength contrast between antigorite and olivine is < 2, which suggests that a thin antigorite layer will have only a weak decoupling effect at the slab–mantle wedge interface.