In studies on the combustion process, thermodynamic analysis can be used to evaluate the irreversibility of the combustion process and improve energy utilization efficiency. In this paper, the combustion process of a laminar oxy-fuel diffusion flame was simulated, and the entropy generation due to the irreversibilities of the radiation process, the heat conduction and heat convection process, the mass diffusion process, and the chemical reaction process was calculated. The effect of the oxygen concentration in the oxidizer on the entropy generation was analyzed. The results indicated that, as the oxygen concentration in the oxidizer increases, the radiative entropy generation first increases and then decreases, and the convective and conductive entropy generation, the mass diffusion entropy generation, the chemical entropy generation, and the total entropy generation gradually increase.