Low concentrations of dissolved oxygen (DO) are usually found in biological anoxic pre-denitrification reactors, causing a reduction in nitrogen removal efficiency. Therefore, the reduction of DO in such reactors is fundamental for achieving good nutrient removal. The article shows the results of an experimental study carried out to evaluate the effect of the anoxic reactor hydrodynamic model on both residual DO concentration and nitrogen removal efficiency. In particular, two hydrodynamic models were considered: the single completely mixed reactor and a series of four reactors that resemble plug-flow behaviour. The latter prove to be more effective in oxygen consumption, allowing a lower residual DO concentration than the former. The series of reactors also achieves better specific denitrification rates and higher denitrification efficiency. Moreover, the denitrification food to microrganism (F:M) ratio (F:MDEN) demonstrates a relevant synergic action in both controlling residual DO and improving the denitrification performance.