This study evaluated the in vitro antiplasmodial and cytotoxic effects of 26 extracts from nine marine sponges collected in Salvador, Bahia state, Brazil. All assayed extracts were found to be potently active against Plasmodium falciparum W2 strain, with IC 50 values ranging from 0.28 to 22.34 μg mL −1 , and weakly cytotoxic against the human cell line WI-26-VA4 with CC 50 values > 89 μg mL −1 , thus displaying selectivity indices (SI) equal or higher than 17. Interestingly, some SI values exceeded 1,000. The highly potent and selective antiplasmodial activity of the assessed marine sponges is reported for the first time in this study.