<p>Neurocryptococcosis is a serious disease that mainly affects individuals with compromised immune systems. However, “immunocompetent” individuals are also affected by this condition even without any known underlying disease or compromised immune system. In this study, we evaluated the CD4 + T lymphocyte population and subpopulations in the peripheral blood of eight hospitalized patients with neurocryptococcosis and eight healthy control individuals. Thus, our objective was to contribute to this understanding by characterizing the T lymphocyte population (CD3 + CD4 +) and subpopulations, with analyses of the activation and regulation status of responsive T cells in naïve (N), central memory (TMC), effector memory (TME), and terminally differentiated effector (TEMRA) in apparently immunocompetent patients and healthy control individuals. Our results showed a significant increase in CD4 + γδ T subpopulations, CD4 + CD25 + CD127^low, CD4 + CD25 + CD127^+high regulatory T cells, CD4 + CD45RA + CCR7- terminally differentiated effector memory (TEMRA) T cells, and CD4 + CD45RA-CCR7- effector memory (TME) T cells. We also observed a significant decrease in total lymphocytes, CD4 + CD45RA + CCR7 + (naïve) T cells, and CD4 + CD45RA-CCR7 + central memory (TMC) T cells. CD4 + T and CD4 + αβ T cells did not show statistically significant differences between the study groups. These results suggest that the immune response of these patients is undergoing alterations in the maturation and differentiation of T lymphocytes and may be related to the virulence factors of the fungus that interfere in several mechanisms of the cells of both the innate and adaptive immune response, as well as with possible regulation disorders of T helper subsets immune responses during <i>Cryptococcus</i> infection.</p>