Hemoglobin concentration ([Hb]) is used for the clinical diagnosis of anemia, and in sports as a marker of blood doping. [Hb] is however subject to significant variations mainly due to shifts in plasma volume (PV). This study proposes a newly developed model able to accurately predict total hemoglobin mass (Hbmass) and PV from a single complete blood count (CBC) and anthropometric variables in healthy subject. Seven hundred and sixty-nine CBC coupled to measures of Hbmass and PV using a CO-rebreathing method were used with a machine learning tool to calculate an estimation model. The predictive model resulted in a root mean square error of 33.2 g and 35.6 g for Hbmass, and 179 mL and 244 mL for PV, in women and men, respectively. Measured and predicted data were significantly correlated (p < 0.001) with a coefficient of determination (R-2) ranging from 0.76 to 0.90 for Hbmass and PV, in both women and men. The Bland-Altman bias was on average 0.23 for Hbmass and 4.15 for PV. We herewith present a model with a robust prediction potential for Hbmass and PV. Such model would be relevant in providing complementary data in contexts such as the epidemiology of anemia or the individual monitoring of [Hb] in anti-doping.