Cross-diffusion effects, including Soret and Dufour effects, are enhanced around the pseudo-critical temperature (Tpc) of a binary mixture. Their influences on heat transfer at supercritical pressure have been scarcely studied. To bridge this gap, large-eddy simulations (LES) are conducted to investigate forced convective heat transfer of a CO2–ethane mixture at supercritical pressures in a circular pipe subject to a uniform heat flux. Both heating and cooling conditions, along with varying initial concentrations and thermodynamic pressures, are included in the simulations. The LES results reveal that the Soret effect causes concentration separation, resulting in a concentration boundary layer. The magnitudes of the thermodiffusion factor (kT) and the radial temperature gradient control the intensity of separation, which is more pronounced at near-critical pressure and high heat flux. Since kT is significant only around Tpc, downstream decay of the concentration separation is observed as the loci of T=Tpc migrate away from the wall so that the local radial temperature gradient diminishes. The primary factors affecting heat transfer are the variations in thermal conductivity and isobaric specific heat resulting from concentration separation. In contrast, the Dufour effect and the accompanying inter-diffusion play negligible roles. In deterioration scenarios, the bulk Nusselt number (Nub) shows a maximum relative drop of 8%, whereas in enhancement scenarios, Nub shows a maximum relative increase in 10%, with both deterioration and enhancement decaying downstream. Cross-diffusion effects have negligible impacts on density and streamwise velocity, but noticeably alter streamwise velocity fluctuation and turbulent kinetic energy.