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In this study, the chemical composition and antimicrobial activity of the essential oil (EO) extracted from leaves of the Moroccan endemic plant Argania spinosa were investigated for the first time, to the best of our knowledge. In addition, the EO antimicrobial activity was evaluated in combination with two known antibiotics (ciprofloxacin and fluconazole), in order to ascertain possible synergistic effects. The chemical composition analyzed by GC/MS showed that A. spinosa EO was characterised by the abundance of geranyl acetate (19.1