Anemia is defined according to decreased blood hemoglobin concentration ([Hb]), which is considered a marker of low total red blood cell volume (RBCV). Alterations of plasma volume (PV) may also modify [Hb] without concomitant changes in RBCV. Since anemia and fluid retention are frequent complications of chronic kidney disease (CKD), we hypothesized that anemia during CKD may in part be related to expanded PV without a simultaneous decrease in RBCV. We quantified hemoglobin mass, RBCV, PV, and total blood volume (BV) using an automated carbon monoxide device in 40 consecutive stage 3-5 CKD patients not on dialysis and in seven healthy male controls of the same age range. These were compared within and to predicted volumes according to Nadler's formula. Arterial stiffness and NT-proBNP were measured. RBCV was similar to predicted values range in anemic CKD patients 2073 (1818-2704) versus, 2061 (1725-2473) mL, P > 0.05. In contrast, PV was largely increased in anemic CKD patients (3881 (3212-4352) vs. 2916 (2851-3201)), P = 0.01. Of 26 anemic patients, only six had a >20% decrease in RBCV as the cause for their anemia, whereas 14 had a >20% increase of PV as a cause for their anemia. NT-pro BNP correlated with eGFR but neither with PV nor BV, whereas arterial stiffness was not correlated to blood volumes. Anemia in CKD as diagnosed by low [Hb] is not necessarily associated to low RBCV but may reflect increased PV. This finding has implications for the treatment of CKD patients and may refrain from normalizing [Hb] levels in all CKD patients.