Paraconiothins A-J (1-10), 10 new sesquiterpenoids, as well as five known sesquiterpenoids, were isolated from the cultures of the endophytic fungus Paraconiothyrium brasiliense ECN-258. The structures of the sesquiterpenoids were elucidated by extensive spectroscopic analysis. Furthermore, the absolute structures of 7 and 8 were determined by comparing their experimental and computed electronic circular dichroism data. Paraconiothins A-G (1-7) were eremophilane sesquiterpenoids, while paraconiothins H-J (8-10) had new or rare carbon frameworks that are possibly biosynthesized by a pathway involving the rearrangement of eremophilane sesquiterpenoids. Paraconiothins C (3) and I (9) exhibited an inhibitory effect on the liver X receptor α at a concentration of 50 μM.