Recording the relative blood volume is a standard feature of modern dialysis devices, enabling feedback guidance of ultrafiltration and dialysate conductivity. Technically, the process is based on optical or ultrasonic methods. On the grounds of clinical evidence suggesting a malfunction of the optical hemoglobin (Hb)-dependent absorbance method in the presence of sodium changes, we compared the system with the ultrasonic method. Six patients underwent hemodialysis with a step sodium profile (140, 150, 130, and 140 mmol/L, hourly switch), with two dialysis devices featuring the optical and the ultrasonic blood volume detector, respectively. The ultrasonic system recorded a decreasing blood volume throughout the treatment. With the optical method, changes in dialysate sodium led to inverse deviations of the blood volume curve. In another treatment without profile administering, a bolus of hypertonic sodium led to the detection of a rapid 8.7% reduction in blood volume with the optical method, which was not observed with the ultrasonic device. Blood volume monitors using the optical absorbance device are influenced by osmotic changes. An increase in osmolality produces a paradox drop in the measured blood volume and vice versa rendering the monitor inappropriate for use in sodium profiling.