A method of operating a redox flow battery, may include maintaining a positive electrode compartment pressure greater than a negative electrode compartment pressure, and maintaining a cross-over pressure less than a membrane break-through pressure, wherein the cross-over pressure equals the negative electrode compartment pressure subtracted from the positive electrode compartment pressure. In this way, ionic resistance across the separator can be maintained at a lower level by reducing gas bubbles trapped therein while reducing separator break-through, thereby increasing performance of the redox flow battery system.