Secondary metabolites play a crucial role in marine invertebrates chemical ecology, and it is thus of great importance to understand factors regulating their production and sources of variability. This work aimed to study the bromotyrosine derivatives variability in the Mediterranean sponge Aplysina cavernicola and to better understand how biotic (reproductive state) and abiotic factors (seawater temperature) could partly explain this variability. Results showed that A. cavernicola reproductive cycle has little effect on the variability of the sponge secondary metabolism, whereas water temperature has a significant influence on the production level of secondary metabolites. Analysis of the temporal variability of the sponge methanolic extracts bioactivity showed that bioactivity variability was related to the presence of the minor secondary metabolite dienone, which accounted for 50% of the bioactivity observed. Further bioassays coupled to HPLC extract fractionation confirmed that dienone was the only compou