Uranium is traditionally stabilized in its ductile γ (BCC) phase by the addition of elements such as Mo, Nb or Zr (Mo is used in metallic fuel for reactor applications). Due to the resemblance of uranium alloys to ferrous alloys, an attempt was made to synthesize single phase U-based high entropy alloys (HEAs) in the U-Mo-Nb-Zr system, following empirical rules related to enthalpies of mixing and atomic radius differences. Microstructure, phase and elemental compositional were characterized, and mechanical properties were measured. This research showed that despite the expectation that a single γ (BCC) phase would be formed, these alloys usually presented two-phase structures; a U-rich γ phase and a Mo-Nb rich BCC phase or a Laves phase. Thermodynamic calculations were successful in predicting the content of phases in the alloys but were not in full agreement with the experimental results. Small punch tests (SPT) showed that most of the studied samples were hard and brittle, which could be attributed to the presence of the Laves phases or alternatively, could be correlated with the multi-component γ (BCC) phase, since other BCC HEAs also tend to be hard and brittle.