Interleukin (IL)–27 is a heterodimeric cytokine with potent inhibitory properties. Thus, mice that lack IL–27–mediated signaling develop exaggerated inflammatory responses during toxoplasmosis as well as other infections or autoimmune processes. While regulatory T (Treg) cells are critical to limit inflammation, their role during toxoplasmosis is controversial because this infection results in a dramatic decrease in the total numbers of these cells associated with reduced levels of IL–2. Because IL–27 suppresses IL–2, we initially hypothesized that it was responsible for the Treg cell “crash”. Thus, we examined the role of IL–27 and IL–2 and their effects on Treg cells during toxoplasmosis. We observed that although IL–2 production is enhanced in the absence of IL–27, this was not sufficient to rescue Treg cell frequencies during infection. Rather, our data indicated that IL–27 promoted an immunosuppressive Treg cell population that displayed a T helper 1 (TH1) phenotype, characterized by the expression of T–bet, CXCR3, IL–10 and interferon (IFN)–γ. Although IFN–γ and IL–27 can give rise to a population of T–bet+ Treg cells in vitro, there were distinct differences in the signaling and transcriptional responses of Treg cells to these cytokines. Analysis of the genes induced by IL–27 revealed that it promoted Treg cell expression of a number of inhibitory receptors such as LAG–3 and PD–1 which function to limit the magnitude of T cell responses. Taken together, these studies highlight the role of IL–27 as a central coordinator of Treg cell effector functions during inflammation.