A hypersonic, spatially evolving turbulent boundary layer at Mach 12.48 with a cooled wall is analysed by means of direct numerical simulations. At the selected conditions, massive kinetic-to-internal energy conversion triggers thermal and chemical non-equilibrium phenomena. Air is assumed to behave as a five-species reacting mixture, and a two-temperature model is adopted to account for vibrational non-equilibrium. Wall cooling partly counteracts the effects of friction heating, and the temperature rise in the boundary layer excites vibrational energy modes while inducing mild chemical dissociation of oxygen. Vibrational non-equilibrium is mostly driven by molecular nitrogen, characterized by slower relaxation rates than the other molecules in the mixture. The results reveal that thermal non-equilibrium is sustained by turbulent mixing: sweep and ejection events efficiently redistribute the gas, contributing to the generation of a vibrationally under-excited state close to the wall, and an over-excited state in the outer region of the boundary layer. The tight coupling between turbulence and thermal effects is quantified by defining an interaction indicator. A modelling strategy for the vibrational energy turbulent flux is proposed, based on the definition of a vibrational turbulent Prandtl number. The validity of the strong Reynolds analogy under thermal non-equilibrium is also evaluated. Strong compressibility effects promote the translational–vibrational energy exchange, but no preferential correlation was detected between expansions/compressions and vibrational over-/under-excitation, as opposed to what has been observed for unconfined turbulent configurations.