Pulicaria crispa (syn. Francoeuria crispa Forssk., Cas) is a member of the Compositae prevalent in central Saudi Arabia and used locally to treat inflammation and as an insect repellent. As part of a systematic examination of medicinal plants of Saudi Arabia, prior work yielded the cytotoxic sesquiterpene lactone 2α-hydroxyalantolactone [1] as a major component of the petroleum ether extract of dried aerial parts. Further investigation of the 95% EtOH extract of defatted material yielded a new sesquiterpene lactone epoxide [2], structurally related to [1]. High resolution eims, ir, uv, ¹H-nmr, and ¹³C-nmr data confirmed its structure, and epoxidation of [1] with mchloroperbenzoic acid (MCPBA) yielded a product identical to [2], confirming it as 2α-hydroxy-5α,6α-epoxyalantolactone. Compound [2] was cytotoxic to KB cells (ED₅₀=0.4 μg/ml), similar to [1] (ED₅₀=0.33 μg/ml), while its acetate [4] showed higher cytotoxicity (ED₅₀=0.05 μg/ml). A flavonoid axillarin [5] was also isolated, with ¹³C-nmr data reported for the first time. Axillarin exhibited activity in a screen for potential carcinogenesis inhibitors, decreasing benzo(a)pyrene metabolism in cultured hamster embryo cells by an average of 61.3% at 25 μg/ml medium, indicating potential as a chemopreventive agent, with further animal studies underway.