This paper reports the first Computational Fluid Dynamics (CFD) model developed for biomass pyrolysis oil spray combustion using Finite-Rate Chemistry (FRC) approach. To make the CFD calculations feasible, a reduced mechanism for modeling the combustion of biomass Fast Pyrolysis Oil (FPO) based on the POLIMI 1412 mechanism and a model for eugenol oxidation was developed. The reduced mechanism consisted of 200 reactions and 71 species. This level of complexity was found to be a good tradeoff between predictive power and computational cost such that the reduced model could be used in CFD modeling. The predictive power of the reduced mechanism was demonstrated via 0D (adiabatic, premixed, constant pressure reactor), 1D (laminar counterflow flame) and 3D (CFD of a methane-air flat-flame piloted FPO spray flame) calculations. Results from CFD were compared against experimental data from non-intrusive optical diagnostics. The reduced model was successfully used in CFD calculations—the computational cost was approximately 2 orders of magnitude higher than that of a simplified model. Using the reduced mechanism, the concentration of pollutants, minor combustion products, and flame radicals could be predicted—this is added capability compared to already existing models. The CFD model using the reduced mechanism showed quantitative predictive power for major combustion products, flame temperature, some pollutants and temperature, and qualitative predictive power for flame radicals and soot. © 2021 The Authors