Further research on the constituents of the sponge Axinyssa isabela collected in the Gulf of California has led to the isolation of nine new sesquiterpenes, the eudesmanes axinisothiocyanates M and N (1, 2), the bisabolane axinythiocyanate A (3), and the aristolane derivatives axinysones A-E (4-8) and axinynitrile A (9), together with four known sesquiterpenoids (10-13). The structures of the new metabolites have been established by spectroscopic techniques.The absolute configuration of axinysones A (4) and B (5) has been assigned after esterification with (R)- and (S)-MPA acids. In addition, the unusual nitrile-containing sesquiterpene 9 has been synthesized from (+)-aristolone (14). The cytotoxic activity of the compounds isolated has been tested against three human tumor cell lines.