We determined the chemical composition and investigated the antifungal activity of Otacanthus azureus (Linden) Ronse essential oil alone or combined with azoles antifungals against a range of human yeasts and dermatophytes. The oil was shown to be composed in majority of sesquiterpenes. Using broth microdilution techniques, it was found to exert interesting in vitro antifungal activities, more particularly against human dermatophytes, with minimum inhibitory concentrations as low as 4µg/ml against a clinical isolate of Trichophyton rubrum. The analysis of the combined effect of this oil with azoles highlighted a pronounced synergism between the oil and ketoconazole or itraconazole, against Candida albicans, C. parapsilosis and Trichophyton mentagrophytes, with fractional inhibitory concentration indices in the 0.1–0.5 range. Interestingly, the oil showed no cytotoxicity on VERO cells (ED50>100µg/ml). According to these results, O. azureus essential oil may be considered a promising natural product in the treatment of human mycoses, more particularly those originating from dermatophytic fungi. Also, it is likely to reduce the minimum effective dose of ketoconazole and itraconazole against Candida species, thus minimizing the side effects of these drugs, and the risk to develop resistances.