Eight previously undescribed sesquiterpenoids, tremutins A-H (<b>1</b>-<b>8</b>), together with three known ones (<b>9</b>-<b>11</b>), were isolated from cultures of the basidiomycetes <i>Irpex lacteus</i>. Structures of the new compounds together with absolute configurations were elucidated on the basis of extensive spectroscopic methods, as well as single-crystal X-ray diffractions and equivalent circulating density calculations. Compounds <b>1</b> and <b>2</b> possess an unusual 6/7-fused ring system that might be derived from a tremulane framework. Compounds <b>3</b>-<b>7</b> and <b>9</b>-<b>11</b> are tremulane sesquiterpenoids of which <b>4</b> and <b>5</b> are the first tremulane examples with a 1,2-epoxy moiety to be reported. Compounds <b>6</b>, <b>7</b>, <b>10</b>, and <b>11</b> possess weak activities to several human cancer cell lines. Compound <b>8</b> shows a weak inhibitory effect on NO production with a half maximal inhibitory concentration (IC<sub>50</sub>) value of 22.7 μM. Compound <b>1</b> inhibits the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells with an IC<sub>50</sub> value of 22.4 μM, while <b>2</b> inhibits concanavalin A (Con A)-induced T cell proliferation and LPS-induced B lymphocyte cell proliferation with IC<sub>50</sub> values of 16.7 and 13.6 μM, respectively.