Candida parapsilosis is the third most frequent cause of candidemia. Despite its clinical importance, little is known about the human immunological response to C. parapsilosis. In this study, we compared the cytokine responses evoked by Candida albicans and C. parapsilosis. C. parapsilosis–stimulated human peripheral blood mononuclear cells (PBMCs) produced similar quantities of tumor necrosis factor α and interleukin 6 and slightly lower amounts of interleukin 1β, compared with C. albicans–stimulated cells. PBMCs stimulated with C. parapsilosis displayed a skewed T-helper cell response, producing more interleukin 10 and less interferon γ than cells stimulated with C. albicans. Notably, C. parapsilosis induced much less interleukin 17 and interleukin 22 production as compared to C. albicans. Inhibition of the 3 classical mitogen-activated protein kinases (p38 kinase, ERK, and JNK) revealed kinase-dependent differences in reductions in cytokine production by the 2 Candida species. Decreased cytokine production after inhibition of dectin 1 revealed that this receptor plays a major role in the recognition of both C. albicans and C. parapsilosis. These data improve understanding of the immune response triggered by C. parapsilosis, a first step for the future design of immunotherapeutic strategies for these infections.