Multi-principal element alloys (MPEAs) are alloys that form stable solid solution phases with three or more principal elements on simple underlying lattices. They are considered to have intermediate structural and chemical complexities between single-element regular metals and multi-element disordered metallic glasses. Due to their unique microstructures and chemical compositions, MPEAs exhibit excellent mechanical properties such as high strength at elevated temperature. Improving mechanical properties of MPEAs requires knowledge of their plastic deformation, at the core of which is dislocation slip. In metals, dislocation slip is intimately connected to the generalized stacking fault energies (GSFEs) and local slip resistances (LSRs). In this work, we conduct atomistic calculations to obtain GSFEs and LSRs on three slip planes – {110}, {112}, and {123} – in three refractory MPEAs that attain high melting temperatures. We find that the three MPEAs have differing values of GSFE and LSR, as well as plasticity anisotropy. The origin of these differences is discussed.