Blood separation systems and methods are provided for detecting lipids in plasma that has been separated from a plasma-containing fluid, such as blood. Plasma is separated from a fluid in a blood separator, with at least a portion of the separated plasma being removed from the blood separator via a plasma flow path. Blue and/or ultraviolet light is passed through the separated plasma in the blood separator or in the plasma flow path, with at least a portion of the light being received after passing through the separated plasma. A signal is generated based on the amount of light passing through the separated plasma, with the signal being indicative of the lipid content of the separated plasma. Determining the lipid content of the separated plasma involves comparing the difference between the signal and a reference signal that represents receipt of all or a pre-selected amount of the light.