A new spiro azaphilone derivative, aspergillusone C (1), and a new cadinane-type sesquiterpenoid, aspergillusone D (2), together with a known azaphilone, felinone A (3), were isolated from the endophytic fungus Aspergillus clavatus. The structures of the new compounds were elucidated by NMR spectroscopy and electron circular dichroism data. Compound 2 exhibited detectable cytotoxic activity against two cell lines (MCF-7 and A549), with IC50 values of 5.9 and 0.2 RM, respectively, in the MTT assay.