<p>Niobium is an important constituent element of refractory multi-principle element alloys (RMPEAs), a promising class of high temperature structural materials. In contrast to many other alloys, RMPEAs made of early transition metals tend to dissolve high concentrations of oxygen, which can have deleterious effects on their properties. A combined first principles and statistical mechanics study is performed to elucidate the electronic and chemical factors that lead to the high oxygen solubility in BCC Nb and the peculiar defect formation in the vacancy-ordered rocksalt NbO monoxide at elevated temperatures.The calculated phase diagram contains eight stable phases: BCC Nb, rocksalt NbO, five Wadsley–Roth structures with stoichoimetries <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\textrm{Nb}_{3}\textrm{O}_{7}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Nb</mtext> <mn>3</mn> </msub> <msub> <mtext>O</mtext> <mn>7</mn> </msub> </mrow> </math></EquationSource> </InlineEquation>, <InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(\textrm{Nb}_{12}\textrm{O}_{29}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Nb</mtext> <mn>12</mn> </msub> <msub> <mtext>O</mtext> <mn>29</mn> </msub> </mrow> </math></EquationSource> </InlineEquation>, <InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(\textrm{Nb}_{22}\textrm{O}_{54}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Nb</mtext> <mn>22</mn> </msub> <msub> <mtext>O</mtext> <mn>54</mn> </msub> </mrow> </math></EquationSource> </InlineEquation>, <InlineEquation ID="IEq4"> <EquationSource Format="TEX">\(\textrm{Nb}_{25}\textrm{O}_{62}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Nb</mtext> <mn>25</mn> </msub> <msub> <mtext>O</mtext> <mn>62</mn> </msub> </mrow> </math></EquationSource> </InlineEquation>, <InlineEquation ID="IEq5"> <EquationSource Format="TEX">\(\textrm{Nb}_{2}\textrm{O}_{5}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Nb</mtext> <mn>2</mn> </msub> <msub> <mtext>O</mtext> <mn>5</mn> </msub> </mrow> </math></EquationSource> </InlineEquation>, and gaseous <InlineEquation ID="IEq6"> <EquationSource Format="TEX">\(\textrm{O}_{2}\)</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mtext>O</mtext> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation>. A high oxygen solubility is predicted in BCC Nb at elevated temperatures. Pairs of interstitially dissolved oxygen in BCC Nb are predicted to repel each other, with Coulomb and closed-shell repulsive interactions being important at short range and strain-mediated interactions extending to longer distances. The vacancy-ordered rocksalt NbO is predicted to tolerate Nb vacancies, leading to a stabilization of oxygen rich concentrations at elevated temperature. Our fundamental study of phase stability in the Nb–O binary provides a foundation for understanding the behavior of oxygen in other BCC metals and in the more complex refractory multi-principle element alloys.</p>