The Sporothrix genus includes important human pathogens that cause sporotrichosis, neglected endemic mycoses with limited therapeutic options. In this study, we demonstrated that ibuprofen, an anti-inflammatory drug, increased the in vitro antifungal activity of itraconazole, the first choice treatment to human sporotrichosis. We evaluated Sporothrix brasiliensis and Sporothrix schenckii species, which are the main etiological agents of sporotrichosis in Brazil. Ibuprofen inhibited the growth of yeasts with minimum inhibitory concentration (MIC) values of 128 µg/ml and 256 µg/ml from S. brasiliensis and S. schenckii, respectively. Ibuprofen showed an increased anti-Sporothrix activity when associated with itraconazole, displaying a synergistic activity. A pronounced increase in the inhibitory activity of itraconazole was observed after association with ibuprofen concentrations higher than 4 µg/ml, in a dose dependent way. The relevant in vitro synergistic activity of ibuprofen with itraconazole highlight the importance of expanding studies about clinical evaluation of this combined therapy, that may improve the treatment of human sporotrichosis.