The response of [100]-oriented single-crystal face-centered-cubic Al-0.1 CoCrFeNi and Al0.3CoCrFeNi high-entropy alloy (HEA) microcrystals tested from 293 to 573 K by means of in situ microcompression is reported. At all temperatures, plasticity is governed by dislocation slip with significant strain hardening and intermittent strain bursts observed. A model, which is in good agreement with experimental measurements, is also developed to predict the effects of Al concentration, temperature, and crystal size on the strength of HEAs. The model interestingly predicts a softening response with an increase in Al concentration when the crystal size is +/- 0.1 mu m. Finally, this model can guide the development of advanced HEAs for small-scale applications. [GRAPHICS IMPACT STATEMENT In situ scanning electron microscopy (5EM) experiments are performed to quantify the thermomechanical response of AIxCoCrFeNi microcrystals. A physics-based model is also proposed to predict the strength of high-entropy alloys as a function of crystal size, temperature, and Al concentration.