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Neuromeningeal cryptococcosis is a life-threatening infection of the central nervous system, caused by encapsulated yeast belonging to the <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complexes. Recent data showed that virulence and antifungal resistance are variable for yeasts belonging to the <i>C. gattii</i> species complex. There is an increase in resistance to fluconazole for yeasts of the <i>C. gattii</i> species complex and the virulence is variable according to the genotype. In the present study, (i) we explored and compared the mechanisms of resistance to fluconazole between <i>C. deuterogattii</i> clinically resistant strains and induced fluconazole-resistant strains by exposure to fluconazole in vitro, and (ii) we studied their virulence in the <i>Galleria mellonella</i> study model. We demonstrated that the fluconazole resistance mechanisms involved were different between clinically resistant strains and induced resistant strains. We also demonstrated that fluconazole-induced resistant strains are less virulent when compared to the original susceptible strains. On the contrary, the clinically resistant strain tested maintains its virulence compared to fluconazole-susceptible strains of the same sequence type.