Systems and methods are provided for separating a red blood cell-containing fluid into separated red blood cells and another fluid constituent. A suitable system includes a disposable fluid flow circuit and a durable, reusable separation system, with the circuit being mounted onto or otherwise associated with the separation system. The circuit includes a membrane separator for separating the fluid into its constituent parts, as well as a leukoreduction filter. The leukoreduction filter may be used before or after the red blood cell-containing fluid has been passed into the membrane separator. The red blood cell-containing fluid (if the leukoreduction filter is positioned upstream of the membrane separator) or the separated red blood cells (if the leukoreduction filter is positioned downstream of the membrane separator) may also be passed through a microaggregate filter prior to passing through the leukoreduction filter.
