An in situ characterization of heterogeneous catalysts under industrial operating conditions may involve high pressure and reactants in both the gas and the liquid phase. In this paper, we describe an in situ XAS flow reactor, which is suitable to operate under such conditions (pmax 20 bar, Tmax 350 °C) and report its use in studying hydrodesulfurization (HDS) catalyst activation. The effect of pressure (1 or 20 bar) and sulfiding agent on the sulfidation rate of a CoMo/Al2O3 catalyst prepared with phosphate and polyethyleneglycol is determined from in situ XANES at the Co and Mo K-edges. Cobalt is sulfided substantially faster in 20 bar compared to 1 bar H2/H2S (gas phase activation), whereas the effect of pressure on molybdenum sulfidation is smaller. Liquid phase activation in 20 bar H2 and a model diesel feed (n-hexadecane/tert-nonylpolysulfide (TNPS)) starts at 190 °C, initiated by the in situ formation of H2S from TNPS, and is rapidly completed. Thus, pressure and sulfiding agent have a substantial effect on the sulfidation rate of HDS catalysts. The in situ XAS approach introduced here enables studying catalysts under industrial operating conditions and is applicable to not only hydrodesulfurization catalysts, but to any other catalytic system that requires high pressure and reactants in a gas/liquid mixture.