This work investigates the influence of hydrocarbon pollution on the performance of desalination membranes with a polysulfone support. Toluene was chosen as the model hydrocarbon compound and permeation measurements were performed on two commercial membranes with a polysulfone support in water saturated with toluene. Over time, the TriSep TS80 membrane under analysis broke down and the delamination of the separation layer was observed. The influence of the polysulfone layer on the membrane deterioration was studied in detail by the use of a model system of a thin polysulfone film on top of a silicon wafer. In situ spectroscopic ellipsometry, and in situ optical microscopy revealed that the non-ideality of the hydrocarbon in water system initiates a dewetting of the polysulfone layer which is the root cause of the membrane failure.