Plasma volume increases rapidly with the initiation of endurance training and is elevated after just one exercise bout (Gillen et al., 1991). An increase in plasma albumin content and plasma osmolality following exercise is likely the main mechanism behind this expansion (Convertino et al., 1980). The augmented plasma volume results in an increased total blood volume and a concomitant transient reduction in hematocrit, often referred to as sports anemia. Only after months of endurance training, hematocrit normalizes as a consequence of the delayed expansion in red blood cell volume. In fact, one mechanism underlying the augmented red blood cell production includes a lowered hematocrit since the reduced arterial oxygen content results in a lower kidney tissue oxygen pressure that stimulates erythropoietin synthesis in the renal peritubular fibroblast-like cells (Montero and Lundby, 2018). However, mechanisms other than renal tissue hypoxia have been related to erythropoietin synthesis and include for instance plasma volume-regulating hormones such as angiotensin II and vasopressin, alterations in central venous pressure or estrogen and testosterone concentrations (Montero and Lundby, 2018). The relevance of these hematological changes for elite performance is highlighted in the fact that the increased plasma and red blood cell volume are major determinants of the improved exercise capacity with endurance training as these lead to greater maximal cardiac output and oxygen transport capacity (Montero and Lundby, 2018). In support of this, elite endurance athletes have greatly expanded blood volumes. Specifically, we found 25% higher total blood volumes in endurance champions than in untrained individuals (Oberholzer et al., unpublished). A large proportion of the volumetric variations was explained by differences in lean body mass which was strongly related to total blood volume (R2=0.81, n=671) (Oberholzer et al., unpublished). The highly vascularized nature of skeletal muscle may justify this relationship, yet the exact mechanisms that explain the association between lean body mass and blood volume are so far unclear. Thus, while a vast amount of research is conducted on the short-term regulation of blood volume with endurance training, the mechanisms underlying the lifelong hematological adaptations in elite endurance athletes are still to be elucidated. In this presentation, current research on the regulation of plasma and red blood cell volume expansion with endurance training is discussed, while influencing factors such as sex differences and age are considered. Furthermore, new cross-sectional data on the core factors that determine the hematological differences between endurance athletes and untrained individuals are presented.