The use of microalgae cultures has been proposed as an innovative method to remove CO2 from biogas. However, the design of a large-scale installations requires the identification of key operational parameters and the determination of the maximum treatment capacity of the system. The aim of this work is to advance in that direction, using mathematical modelling. A model was developed, considering a system composed of a bubble column connected with an open photobioreactor. Simulations were carried out to evaluate the operation of a potential large-scale system. Results show that biogas upgrading would be feasible at large scales. At a biogas treatment capacity of 0.12 m3 d−1 per m3 reactor, an upgraded biogas with less than 3 and 1% of CO2 and O2, respectively, could be obtained. Under such condition, more that 80% of the inorganic carbon from the biogas would be transformed into biomass. Considering the low volumetric capacity of the system, its feasibility is expected to be determined by the biomass economic value.