Modelling and simulation of cascade of membrane separators in series can be helpful in providing useful guidelines for both the design and operational processes. In this work, experimental measurements for air separation by polysulfone hollow fibre membrane permeators in series were used to validate different mathematical models. Single-, two- and three-cell configurations were considered for both co-current and counter-current flow patterns. Experimental results were compared with simulation results of the mixed flow, plug Row, cross-flow, and counter-current mathematical models. Validation parameters included stage cuts, reject depletion, and permeate enrichment. The mixed flow model showed the highest deviations, especially in predicting the reject depletion results. However, it simulated the stage cut results with less deviations. Predictions of the other models matched the measured data closely in most cases. For the co-current flow pattern, results showed that the cross flow model was the best, followed by the plug flow model with some slight differences. Similarly, the counter-current plug Row model performed satisfactorily in simulating the counter current flow configurations. Deviations were found to increase with increasing number of stages. The highest number of errors was given by the reject depletion predictions of the counter-current systems. Deviations were as high as 27% for the mixed flow model and 11% for the counter model. All other deviations were below 10%.