A priming subsystem of a cell processing system carries out a method for priming a spinning membrane separator having an inlet and first and second outlets. The method includes opening a first selectable junction disposed between a priming fluid container and the inlet to open a path between the priming fluid container and the inlet, operating a first pump coupled to the first outlet to draw priming fluid from the priming fluid container into the spinning membrane separator, and closing the first selectable junction and a second selectable junction coupled to the second outlet after drawing the priming fluid into the spinning membrane separator. The method further includes operating the first pump after the first selectable junction is closed to draw a vacuum, and opening the first selectable junction after drawing the vacuum.