The effect of oxygen on the microstructure, mechanical properties and deformation behaviours of as-cast biocompatible Ti40Zr25Nb25Ta10Ox (x = 0.5, 1.0 and 2.0 at.%) high entropy alloys (HEAs) was investigated. All three oxygen-doped HEAs solidified as a single body-centred cubic (BCC) phase grain structure with predominantly high-angle grain boundaries following the Mackenzie prediction. Increasing oxygen content significantly increased tensile strength at a rate of about 180 MPa/1 at.%, but at the expense of tensile ductility. However, with an addition of 0.5% O, the as-cast Ti40Zr25Nb25Ta10O0.5 HEA can achieve a yield strength (σ0.2) of 947 ± 44 MPa and an elongation at break (εf) of 9.5 % ± 1.8 %. These properties make this HEA comparable to medical grade Ti-6Al-4V (wt.%) alloy (ASTM Grade 23 titanium) (σ0.2 ≥ 759 MPa; εf ≥ 10%) in its ability to absorb energy in plastic deformation, but with greater resistance to permanent shape changes. Due to the possible strong interaction between oxygen atoms and dislocations through pinning and de-pinning, all oxygen-doped HEAs exhibited discontinuous yielding, whereas the base HEA underwent normal yielding. No oxygen clusters were detected through atom probe tomography (APT) analysis. The deformation mechanism depends on the oxygen content. The plastic deformation in Ti40Zr25Nb25Ta10O0.5 occurred through the formation of primary and secondary shear bands. In contrast, planar slip bands and a limited number of primary shear bands without secondary shear bands occurred in Ti40Zr25Nb25Ta10O2.0. To ensure sufficient ductility, the oxygen content should be limited to 0.5 at.%. Furthermore, at this oxygen content, the corrosion resistance of the Ti40Zr25Nb25Ta10O0.5 HEA in Hank's solution is comparable to that of Ti-6Al-4V.