The aim of this study was to evaluate the changes in membrane surface properties and solute separation by a nanofiltration membrane during repetitive membrane fouling and chemical cleaning. Secondary treated effluent and model fouling solutions containing humic acids, sodium alginate, or silica colloids were used to simulate membrane fouling. Chemical cleaning was carried out using a commercially available caustic cleaning formulation. Carbamazepine and sulfamethoxazole were selected to examine the filtration behaviour of neutral and negatively charged organic compounds, respectively. Results show that the impact of membrane fouling on solute rejection is governed by pore blocking, modification of the membrane surface charge, and cake enhanced concentration polarisation. Caustic cleaning was effective at controlling membrane fouling and membrane permeability recovery was slightly more than 100%. In good agreement with the literature, the high membrane permeability recovery observed here suggests that caustic cleaning could lead to temporary enlargement of the membrane pores. In addition, microscopic observations based on scanning electron microscopy and energy dispersive spectroscopy revealed some irreversible fouling on the chemical cleaned membrane. Thus caustic cleaning did not completely remove all foulants from the membrane surface and the membrane surface hydrophobicity and zeta potential changed correspondingly. The temporary enlargement of the membrane pores due to caustic cleaning subsequently led to notable changes in the rejection of inorganic salts (measured by conductivity) and carbamazepine. By contrast, the impact of chemical cleaning on the rejection of the negatively charged sulfamethoxazole was negligible. This is because the rejection of sulfamethoxazole is predominantly governed by electrostatic repulsion between the compound and the negatively charged membrane surface and thus is not significantly influenced by any enlargement of the membrane pores.