Abstract The increasing scarcity of potable water increases the demand for non-conventional potable water resources such as desalination. Experiments are carried out using a pilot-scale device of the desalination process for three configurations of membrane allocation inside the pressure vessel. Configuration (A) is one pressure vessel containing one spiral wound membrane (SWM), (B) is four pressure vessels each containing one SWM connected in parallel, and (C) is one pressure vessel containing four membranes connected in parallel. The effect of applied pressure, temperature, and water salinity is studied. Moreover, a mathematical model using ANSYS Fluent was developed and verified using the experimental data. The mathematical model is applied to an idealized case of an actual desalination plant. The main findings are (1) configurations (B) and (C) accomplished higher permeate discharge comparing to (A) by an average percentage of 60 and 50, respectively, while (C) has the lowest output salinity by 30% from configuration (A). (2) The mathematical model is found to reduce the operating pressure of the plant by 8%.