The main objective of this study is to demonstrate the importance of mixing conditions as a source of inconsistencies between half-saturation indices in comparable systems (e.g. conventional activated sludge, membrane bioreactor) when operated at different conditions or different scales. As proof-of-principle, an exemplary system consisting of the second vessel of a hybrid respirometer has been studied. The system has been modeled both using an integrated computational fluid dynamics (CFD)-biokinetic model (assumed to represent the physical system) and a tanks-in-series, completely stirred tank reactor biokinetic model (representing the applied model). The results show that different mixing conditions cause deviations in the half-saturation indices calculated when matching the applied model to the physical system performance. Additionally, sensor location has been shown to impact the calculation of half-saturation indices in the respirometric system. This will only become more pronounced at larger scales. Thus, mixing conditions clearly affect operation and design of wastewater treatment reactors operated at low substrate concentrations. Both operation and design can be improved with the development and application of integrated CFD-biokinetic or compartmental models.