A system is provided for separating a plasma-containing fluid into separated plasma and a concentrated fluid. The system cooperates with a fluid flow circuit including a fluid separation chamber and a plasma outlet line associated therewith for removing separated plasma from the fluid separation chamber. The system includes an optical sensor assembly to monitor the contents of the plasma outlet line and produce an output indicative of the concentration of free plasma hemoglobin in the plasma outlet line. A controller of the system calculates the amount of free plasma hemoglobin in at least a portion of the concentrated fluid based at least in part on the output of the optical sensor assembly. The controller may periodically calibrate the optical sensor assembly by determining an instrument-specific correlation between optic output and free hemoglobin concentration and comparing it to experimentally determined data to ensure continued reliability of the optical sensor assembly.