A system for monitoring and controlling fluid balance during an extracorporeal photopheresis procedure, comprising: a disposable fluid circuit comprising a product container configured to receive a target cell component; a separator configured to work in association with the disposable fluid circuit, the separator comprising a chamber configured to rotate about a rotational axis and convey whole blood from a blood source into an inlet region of the chamber for separation into a red blood cell component, a plasma component, and the target cell component; a microprocessor-based controller in communication with the separator, wherein the controller is configured to: estimate an end-of-procedure fluid balance by calculating a total volume of anticoagulant solution having a citrate concentration to be used for the procedure, wherein the end-of-procedure fluid balance is estimated based on manual or automatic inputs comprising an ACD ratio relating unanticoagulated extracorporeal whole blood to anticoagulant solution, an amount of whole blood to process, a citrate infusion threshold rate, a patient body weight associated with the blood source, and a total blood volume of the blood source; draw anticoagulated whole blood into the disposable fluid circuit and the chamber at a whole blood flow rate; separate the anticoagulated whole blood into the red blood cell component, the target cell component, and the plasma component; direct the target cell component to the product container; treat the product container comprising the target cell component to create a treated target cell component; return to the blood source the treated target cell component, a portion of the red blood cell component remaining in the fluid circuit, and/or a portion of the plasma component remaining in the fluid circuit; and provide a first response action if the end-of-procedure fluid balance estimated is above or below a programmed fluid balance range. a disposable fluid circuit comprising a product container configured to receive a target cell component; a separator configured to work in association with the disposable fluid circuit, the separator comprising a chamber configured to rotate about a rotational axis and convey whole blood from a blood source into an inlet region of the chamber for separation into a red blood cell component, a plasma component, and the target cell component; a microprocessor-based controller in communication with the separator, wherein the controller is configured to: estimate an end-of-procedure fluid balance by calculating a total volume of anticoagulant solution having a citrate concentration to be used for the procedure, wherein the end-of-procedure fluid balance is estimated based on manual or automatic inputs comprising an ACD ratio relating unanticoagulated extracorporeal whole blood to anticoagulant solution, an amount of whole blood to process, a citrate infusion threshold rate, a patient body weight associated with the blood source, and a total blood volume of the blood source; draw anticoagulated whole blood into the disposable fluid circuit and the chamber at a whole blood flow rate; separate the anticoagulated whole blood into the red blood cell component, the target cell component, and the plasma component; direct the target cell component to the product container; treat the product container comprising the target cell component to create a treated target cell component; return to the blood source the treated target cell component, a portion of the red blood cell component remaining in the fluid circuit, and/or a portion of the plasma component remaining in the fluid circuit; and provide a first response action if the end-of-procedure fluid balance estimated is above or below a programmed fluid balance range. estimate an end-of-procedure fluid balance by calculating a total volume of anticoagulant solution having a citrate concentration to be used for the procedure, wherein the end-of-procedure fluid balance is estimated based on manual or automatic inputs comprising an ACD ratio relating unanticoagulated extracorporeal whole blood to anticoagulant solution, an amount of whole blood to process, a citrate infusion threshold rate, a patient body weight associated with the blood source, and a total blood volume of the blood source; draw anticoagulated whole blood into the disposable fluid circuit and the chamber at a whole blood flow rate; separate the anticoagulated whole blood into the red blood cell component, the target cell component, and the plasma component; direct the target cell component to the product container; treat the product container comprising the target cell component to create a treated target cell component; return to the blood source the treated target cell component, a portion of the red blood cell component remaining in the fluid circuit, and/or a portion of the plasma component remaining in the fluid circuit; and provide a first response action if the end-of-procedure fluid balance estimated is above or below a programmed fluid balance range.