We hypothesized that selenium(Se)-enriched polysaccharides would possess superior biological activity when compared to those non-enriched. To verify this hypothesis, we obtained by biotechnological methods a Se-enriched analog of Japanese anticancer drug lentinan and, as a reference, the non-Se-enriched fraction. We tested the effects of the obtained fractions on the proliferation of human peripheral blood mononuclear cells. The results suggested a selective immunosuppressive activity, non-typical for mushroom derived polysaccharides. Both fractions caused significant inhibition of human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. The inhibitory effect was not due to the toxicity of the examined polysaccharides. In normal (HUVEC) or malignant (HeLa) cells tested fractions significantly enhanced cell viability and protected the cells from oxidative stress conditions. However, we observed no effect of the polysaccharide fractions on the production of reactive oxygen species by granulocytes in vitro. The selenium content increased the biological activity of the tested polysaccharide fractions.