Instrumented nanoindentation was conducted on a FeCoCrMnNi high-entropy alloy with a single face-centered cubic structure to characterize the nature of incipient plasticity. Experiments were carried out over loading rates of 25–2500μNs−1 and at temperatures ranging from 22 to 150°C. The maximum shear stress required to initiate plasticity was found to be within 1/15 to 1/10 of the shear modulus and relatively insensitive to grain orientation. However, it was strongly dependent upon the temperature, indicating a thermally activated process. Using a statistical model developed previously, both the activation volume and activation energy were evaluated and further compared with existing dislocation nucleation models. A mechanism consisting of a heterogeneous dislocation nucleation process with vacancy-like defects (∼3 atoms) as the rate-limiting nuclei appeared to be dominant.