Various combinations of Fischer-Tropsch and hydroprocessing catalysts were examined in a single-stage fixed bed reactor. All experiments were performed in a lab scale trickle bed reactor at varying temperatures and modified residence times at a constant pressure of 10 bar and H-2/CO = 2. The effect of Fischer-Tropsch and hydroprocessing catalysts (hydrogenation and acidic compound) and their configuration could be determined. The hydroprocessing is strongly influenced by Fischer-Tropsch conversion. Depending on the hydrogenation compound, either a dual layer or a physical mixture configuration can be beneficial. Ni/ZSM-5, with its low hydrogenation activity and insensitivity toward CO, shows more hydroprocessing in the physical mixture than in the dual layer configuration. The opposite is true for Pt/ZSM-5. The use of Fe as a Fischer-Tropsch catalyst can be advantageous because of the necessary higher temperatures and its CO shift activity which accounts for the higher H-2/CH2 ratios.