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Two important aspects of agriculture intensification are the reduction in the concentration of specific soil minerals that affects livestock production and the increase of agricultural by-products, which produce environmental pollution. In this regard, whey - a cheese by-product-often is considered a wasted-product. Due to its lactose concentration, (4.5%), when whey is discarded without treatment generates a high Biological Oxygen Demand (BOD) and a high Chemical Oxygen Demand (COD). Taking into account these two issues, we developed a whey-based culture medium to produce selenium-enriched Kluyveromyces biomass. Then, we evaluated the effect of its supplementation on calves blood selenium concentration. Kluyveromyces marxianus DSM 11954 and Kluyveromyces lactis DSM 3795 strains were used in this study. Different culture media were prepared using whey as a main component and supplemented with peptone, yeast extract, (NH4)2SO4 and K2HPO4 as appropriate. In the selected whey culture medium, three sodium selenite concentrations between 10-30 μg/mL were tested to produce selenium-enriched biomass. After that, a scaled up to 5 L stirred-tank bioreactor was carried out to increase final yeast biomass levels. Finally, dietary supplementation experiments with selenium-enriched yeast were conducted to increase selenium content in calves. K. marxianus DSM 11954 showed a better growth performance than K. lactis DSM 3795 in a medium composed by whey, (NH4)2SO4 5 g/L, K2HPO4 1 g/L (pH 6.5) so, this strain was chosen to continue the experiments. The results showed that sodium selenite addition at 20 μg/mL was adequate to generate selenium-enriched biomass. Our study demonstrated that whey is an optimal and economical culture medium to produce selenium-enriched- yeast biomass. Also, we proved that 10 days of yeast-biomass supplementation raised blood-selenium level in calves. Fil: Gurdo, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Calafat, Mario Jose. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Noseda, Diego Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Gigli, Isabel. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina