Aims Erythropoiesis is a tightly controlled biological event, but its regulation under non‐hypoxic conditions, however, remains unresolved. We examined whether acute changes in central venous blood pressure (CVP) elicited by whole‐body tilting affect erythropoietin (EPO) concentration according to volume‐regulating hormones. Methods Plasma EPO, angiotensin II (ANGII), aldosterone, pro‐atrial natriuretic peptide (proANP) and copeptin concentrations were measured at supine rest and up to 3 h during 30° head‐up (HUT) and head‐down tilt (HDT) in ten healthy male volunteers. Plasma albumin concentration was used to correct for changes in plasma volume and CVP was estimated through the internal jugular vein (IJV) aspect ratio with ultrasonography. Results From supine rest, the IJV aspect ratio was decreased and increased throughout HUT and HDT respectively. Plasma EPO concentration increased during HUT (13%; P = 0.001, P for linear component = 0.017), independent of changes in albumin concentration. Moreover, ANGII and copeptin concentrations increased during HUT, while proANP decreased. The increase in EPO concentration during HUT disappeared when adjusted for changes in copeptin. During HDT, EPO, ANGII and copeptin concentrations remained unaffected while proANP increased. In regression analyses, EPO was positively associated with copeptin (β = 0.55; 95% CI = 0.18, 0.93; P = 0.004) irrespective of changes in other hormones and albumin concentration. Conclusion Reduction in CVP prompts an increase in plasma EPO concentration independent of hemoconcentration and hence suggests CVP per se as an acute regulator of EPO synthesis. This effect may be explained by changes in volume‐regulating hormones.