Despite their vast composition space and promising properties

little is known about the fundamental mechanical behavior of high entropy oxides (HEOs). Here we provide experimental evidence of the nanoscale origin of room temperature deformation in (Co

Cu

Mg

Ni

Zn)O HEOs with different grain sizes. We find that micron-grain (Co

Cu

Mg

Ni

Zn)O deforms predominately through extensive 12110{1–10} dislocation slip manifesting as discrete slip bands. Nano-grain (Co

Cu

Mg

Ni

Zn)O

in addition to moderate dislocation slip activity

deforms through grain boundary sliding and intergranular cracking. The significant dislocation-mediated deformation and grain size dependent behavior demonstrates that HEOs have the potential for diverse and highly tailorable mechanical behavior.