Résumé : Aims: Evaluation of the antibacterial activity of cultivable bacteria associated with the marine sponges Hymeniacidon perlevis and Halichondria panicea against multi-drug–resistant Staphylococcus aureus. Methods and Results: One hundred and fourteen bacterial isolates were recovered from H. perlevis and H. panicea. Antibacterial action was demonstrated by 70% of the isolates against reference strain Staphylococcus aureus ATCC 29213 and by 31·6% against Pseudomonas aeruginosa ATCC 27853 in agar overlay assays. Antibacterial potential was further analysed against 36 multi-drug–resistant hospital Staphylococcus aureus strains with diverse resistance profiles. Among the 80 isolates positive against S. aureus ATCC 29213, 76·3% were active against at least one clinical S. aureus pathogen and 73·6% inhibited one or more methicillin-resistant (MRSA) and vancomycin non-susceptible S. aureus strains. In addition, 41·3% inhibited all vancomycin nonsusceptible MRSA strains. Conclusions: Culturable bacteria associated to H. perlevis and H. panicea are promising sources of antibacterial compounds of great pharmaceutical interest. Significance and Impact of the Study: This study was the first to explore the antibacterial potential of culturable bacteria associated with the marine sponges H. perlevis and H. panicea against MDR bacteria. This is the first report of antibacterial activity by Aquimarina, Denitrobaculum, Maribacter and Vagococcus isolates against MDR S. aureus strains, including vancomycin nonsusceptible and methicillin-resistant ones, against which new antibiotics are urgently needed.