Numerous marine organisms, including macroalgae, produce bioactive compounds. As chemical extraction processes do not distinguish between compounds originating from the alga and its associated microflora, a key step immediately prior to isolation of molecules, is elimination of epibionts from the alga studied. In chemical, ecological and biotechnological contexts, a clear identification of the source organism, when symbiotic interactions occurs, is crucial. We aimed to improve understanding of specific secondary metabolite production by macroalgae through development of a metho-dology for removing microbial epibionts immediately prior to chemical extraction without damaging algal cell surfaces (to avoid extraction of endogenous macroalgal compounds at this stage). Various solutions were tested: non-polar solvents (dichloromethane and hexane), alcohols (methanol, ethanol and isopropanol), oxidants (sodium hypochlorite, hydrogen peroxide and iodine) and a natural product (tea tree oil) at various concentrations and contact times. Five macroalgal species were employed: Chondrus crispus , Fucus serratus , Palmaria palmata , Saccharina latissima and Ulva lactuca . Scanning electron microscopy was used to evaluate the surface integrity. The best epibiont removal rate without damaging tissue was obtained with mixtures of ethanol (40–50%) and sodium hypochlorite (1%). Interestingly, macroalgal moisture content influenced treatment efficacy.