Marine environments represent a great opportunity for the discovery of compounds with a wide spectrum of bioactive properties. Due to the privileged conditions of natural selection, marine natural products are subject to overcome the pressure put on identify novel drugs; not only in the case of newly discovered bioactive metabolites, but also in those previously known. Since drug resistance has caused an increase in infections caused by tuberculous and nontuberculous Mycobacteria, the re-evaluation of known bioactive metabolites has been suggested as a means to address this problem. In this sense, this study presents an evaluation of in vitro effect of laurinterol (1) and aplysin (2), two brominated sesquiterpenes isolated from Laurencia johnstonii against nine Mycobacterium tuberculosis strains and six nontuberculous mycobacteria. Laurinterol (1) exhibited good anti-tuberculous activity, especially against nontuberculous mycobacteria, being remarkable the effect against M. abscessus with MIC values lower than the reference drug imipenem. This study provides further evidence for the antimycobacterial activity of some sesquiterpenes from L. johnstonii, that can be considered an interesting lead compound for the discovery of novel antimycobacterial molecules to treat NTM infections.