Natural cembranoids have shown Quorum Sensing Inhibitory (QSI) activity, but their structure-function interactions are not well understood. Thirty-four cembranoid analogues were synthesized using six natural cembranoids (1-6) previously isolated from the Colombian Caribbean octocorals Eunicea knighti and Pseudoplexaura flagellosa as lead compounds. The analogues (7-40) obtained through the selected chemical transformations were tested in vitro against the QS systems of a Chromobacterium violaceum biosensor. Half of the cembranoid analogues assayed showed superior QSI activity to the lead compounds; three (8, 13, and 18) displayed remarkable potency up to three times higher than the natural compounds. Thereby, we have synthesized a pool of cembranoid QS inhibitors that can be used in concert with natural compounds to develop antipathogenic drugs and antifouling agents.