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The Cryptococcus neoformans and Cryptococcus gattii species complexes are the etiological agents of cryptococcosis, a disease responsible for 181 000 deaths annually worldwide due to late diagnosis and limited treatment options. Studies focusing on the identification of new substances with antifungal activity, such as essential oils (EOs), are urgently needed. While the antifungal effects of EO have already been suggested, their mechanism of action at the molecular level still requires evaluation. In this work, we assessed the molecular changes induced by the exposure of Cryptococus neoformans (H99) and Cryptococcus deuterogatti (R265) to lavender essential oil (LEO) using a morphological and proteomics approach. The identified proteins were categorized by Gene Ontology according to biological processes and molecular functions, and Kyoto Encyclopedia of Genes and Genomes pathway analysis was also conducted. Our findings indicate that LEO creates a stressful environment in both strains; however, the response to this stimulus differs between the two species. In C. neoformans, changes were observed in energy metabolism and pathways related to alternative sources of energy and oxidative stress response. In C. deuterogatti, changes were identified in pathways related to cellular architecture, implying that the cell underwent morphological changes such as membrane and cell wall stiffening. [ABSTRACT FROM AUTHOR]