Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a key role in the pathogenesis of autoimmune diseases and is an important constituent of the human immune response to infection. We report the case of a 45-year-old man with psoriatic arthritis, receiving treatment with infliximab, who presented with high-grade fever, rigor, splenomegaly, acute reactive proteins, and pancytopenia. The diagnosis of visceral leishmaniasis was established. The patient reported that his dog died from Leishmania infection 5 years ago, while he was living in an area endemic for Leishmania. The use of anti-TNF biologic agent in this patient might result in new infection or reactivation of a latent infection with Leishmania, 5 years after the exposure. A detailed current and past medical history should be obtained of every patient candidate for treatment with biologic agents, and a close monitoring is needed for serious opportunistic infections, including visceral leishmaniasis.