Although reverse osmosis (RO) currently dominates the global desalination market, membrane fouling remains a major operational obstacle, which penalizes sustainable plant operation. This study explores a new membrane cleaning technique that uses a saturated CO2 solution to alleviate membrane fouling caused by organic matter, without any additional chemicals. When the CO2 saturated solution is injected into the membrane module at a given pressure, CO2 bubbles start nucleating throughout the membrane surface. This phenomenon is intensified underneath the deposited foulants. The porous structure of the foulants presents cavities, which are considered as imperfection sites that act as a substrate for CO2 bubbles nucleation, leading to an effective membrane cleaning. In this study, sodium alginate, a model polysaccharide, was mixed with different concentrations of Ca2+ to evaluate the cleaning efficiency of the CO2 technique under severe operating conditions when formed Ca2+/alginate fouling layers significantly impend the RO process performance. Furthermore, the effect of hydrodymamic conditions and CO2 saturation pressure on efficiency of permeate flux recovery and membrane morphology is also evaluated and the results are compared to those achieved with Milli-Q water and acidic solution at pH 4 cleanings. Better permeate flux recoveries were observed at higher Ca2+ concentrations comparing to fouling expriments at lower concentrations. The observed effect was attributed to a transition from the gel layer to a looser cake layer which makes CO2 bubble nucleation and subsequent permeate flux recovery more effective due to the presence of a larger number of CO2 nucleation sites as a result of a formation of more porous fouling structures. Permeate flux recovery increased with the increase in cleaning time, cross-flow velocity and CO2 saturation pressure.