The single-stage combination of Fischer-Tropsch synthesis and hydroprocessing without intermediate product fractionation has been studied using Co/Al2O3 as FT and Ni/ZSM-5/gamma-Al2O3 as HP catalysts either in dual-layer arrangement or in physical mixture. Furthermore, the performance of the hydroprocessing catalyst under Fischer-Tropsch conditions was investigated in more detail in the gas phase hydroprocessing of n-dodecane in the presence of CO and H2O vapor, mimicking 69.4% Fischer-Tropsch conversion. All experiments were conducted at 10 bar and varying temperatures and residence times. In the gas phase hydroconversion of n-dodecane, CO and H2O showed a strongly inhibiting effect. The disturbance of the hydrogenation function by CO is most detrimental because enduring deactivation by coke formation is initiated. In combined single-stage experiments, the formation of a liquid hydrocarbon film in the FT reactions reduces the impact of the inhibitors to a large extent. Here, the hydroprocessing performance is mostly determined by the ratio H-2/hydrocarbons. In both single-stage configurations, lower C numbers and larger isomer fractions as compared to the FT reference evidenced the activity of the HP catalyst. In physical mixture configuration, however, the HP catalyst benefits from the higher H-2/hydrocarbon ratios along the complete catalyst bed, resulting in a more efficient reduction of C21+ hydrocarbons and high isomer fractions in a broader range of carbon numbers.