Abstract Platelets are known to have immunomodulatory properties. They modulate immune responses of leukocytes against various pathogens, including fungi. Candida albicans can cause systemic infection in immunocompromised individuals that is associated with a high mortality and morbidity. In the current study, we explored the role of platelets in antifungal host defense against C. albicans. PBMCs were stimulated with heat-killed (HK) C. albicans in the presence or absence of isolated washed platelets. Cytokines were quantified from culture supernatants by ELISA. Inhibition of platelet receptors and cytokine pathways were used to elucidate the mechanisms involved in platelet–leukocyte interaction. In the presence of platelets, PBMCs produced less IFN-γ upon stimulation with HK C. albicans. This effect was dependent on the direct contact between platelets and leukocytes but was independent of the platelet GPIb and P-selectin receptors. The attenuation of IFN-γ was not a direct effect on T cells but was dependent on the presence of APC and T cells. Platelets did not modulate the Th-1–polarizing cytokines IL-12 and IL-18. The addition of PG (PGE2) further diminished IFN-γ levels in PBMCs, and supplementation of cells with nonsteroidal anti-inflammatory drugs was able to restore the level of IFN-γ. Overall, we show that modulation of the Th1 response against C. albicans by platelets is dependent on PGs.