The antiplasmodial activities of sixty norcantharidin analogs were tested in vitro against a chloroquine sensitive (D6, Sierra Leone) and chloroquine resistant (W2) strains of Plasmodium falciparum. Forty analogs returned IC50 values <500μM against at least one of the P. falciparum strains examined. The ring open compound 24 ((1S,4R)-3-(allylcarbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid) is the most active aliphatic analog (D6 IC50=3.0±0.0 and W2 IC50=3.0±0.8μM) with a 20-fold enhancement relative to norcantharidin. Surprisingly, seven norcantharimides also displayed good antiplasmodial activity with the most potent, 5 returning D6=8.9±0.9 and W2 IC50=12.5±2.2μM, representing a fivefold enhancement over norcantharidin.