This study aims to investigate the impacts of chemical cleaning on the performance of a reverse osmosis membrane. Chemicals used for simulating membrane cleaning include a surfactant (sodium dodecyl sulfate, SDS), a chelating agent (ethylenediaminetetraacetic acid, EDTA), and two proprietary cleaning formulations namely MC3 and MC11. The impact of sequential exposure to multiple membrane cleaning solutions was also examined. Water permeability and the rejection of boron and sodium were investigated under various water fluxes, temperatures and feedwater pH. Changes in the membrane performance were systematically explained based on the changes in the charge density, hydrophobicity and chemical structure of the membrane surface. The experimental results show that membrane cleaning can significantly alter the hydrophobicity and water permeability of the membrane; however, its impacts on the rejections of boron and sodium are marginal. Although the presence of surfactant or chelating agent may cause decreases in the rejection, solution pH is the key factor responsible for the loss of membrane separation and changes in the surface properties. The impact of solution pH on the water permeability can be reversed by applying a subsequent cleaning with the opposite pH condition. Nevertheless, the impacts of solution pH on boron and sodium rejections are irreversible in most cases.