Aqueous ethanol extracts of powdered twigs of Euphorbia esula afforded 16 new diterpenoids, named euphorbesulins A-P. These euphorbesulins included presegetane (1-3), jatrophane (4-14), paraliane (15), and isopimarane (16) diterpenoids as well as six known analogues. Compounds 1-3 represent a rare type of presegetane diterpenoid. Their structures were determined by analysis of the spectroscopic data, and the absolute configuration of 1 was established by X-ray crystallography. Diterpenoid 7 showed low nanomolar antimalarial activity, while the remaining compounds showed only moderate or no antimalarial activity.