This study, sought to assess the effect of Selenium (Se) supplementation on wine yeast growth, fermentation efficiency, antioxidant activities and retention of the chromatic properties of mulberry wine. Mulberry musts with three different concentration of Se-enriched yeast were subjected to a 7 days alcoholic fermentation. Post-fermentation quality parameters including phytochemical, chromatic, total residual Se and antioxidant properties were then evaluated. The results showed that, yeast's Se tolerance was exposure time and concentration dependent. This commensurate the increase in percentage efficiency (82.58 ± 0.66–99.07 ± 0.21). Se treated samples exhibited a significant (p < 0.05) improvement in the phytochemical properties and radical scavenging activities to the control. Variations in chromatic properties were correspondingly influenced by changes in concentration of phytochemicals and Se. In general, increasing Se concentration had no significant adverse effect on fermentation efficiency and overall quality. However, it was evident that mulberry wine fermented at 28 °C for 150 h with 100 μg Se, gave the best results with high percentage (65.16%) Se retention in final wine sample.