Artemisinin and its semisynthetic derivatives (1,2,4-trioxanes) are potent antimalarials, and at high concentrations, are also cytotoxic to a variety of cancer cell lines. Synthetic ozonides (1,2,4-trioxolanes) are effective antimalarials that also contain a peroxide pharmacophore, but these compounds have not been tested against cancer cell lines. In this study, we measured the effects of 25 ozonides on Raji lymphoma cell viability using the MTT assay. Eight of the compounds greatly decreased cell viability at 10 μM while the remainder had limited to no effect. A computational analysis was performed to determine the common structural features of the most active compounds. All of the most active compounds contain an ionizable amine with a narrowly defined distance between the ionizable amine and the trioxolane heterocycle. The fifteen compounds with low activity did not fit these criteria. The two compounds with intermediate activity may form an intramolecular H-bond, effectively reducing their activity against the lymphomas.