Blood separation systems and methods are provided for separating blood under conditions of reduced plasma clarity. The system may assess plasma clarity by monitoring light transmissivity of plasma or comparing an actual plasma flow rate to an ideal plasma flow rate, with a low flow rate indicating decreased clarity, which may be addressed by increasing the plasma flow rate. For extracorporeal photopheresis, plasma clarity may be a factor in determining the dosage of irradiating light to apply to mononuclear cells. A fluid processing assembly for mononuclear cell collection may include visual indicium, which an operator may use to determine when to end mononuclear cell collection. The system may detect red blood cells flowing toward a mononuclear cell collection container and reverse the direction of flow to prevent red blood cells from entering the container. An operator may also be enabled to selectively begin and/or end harvesting of mononuclear cells.
