Iron is an essential nutrient for almost all organisms, but it is also a potent toxin because it can catalyze oxidative reactions that are destructive to cells. Transferrin is an essential protein involved in iron metabolism, immunity, and vitellogenesis in insects. We have characterized a cDNA encoding a putative iron-binding transferrin (SpliTrf) in Egyptian cotton leaf worm, Spodoptera littoralis (Lepidoptera: Noctuidae), an important pest that causes extensive losses in many vegetable, fodder, and fiber crops. The structure of the putative SpliTrf showed significant homology to other insect transferrins. Gene expression of SpliTrf was examined from different adult tissues including the fat body, midgut, Malpighian tubules, nervous system, hemolymph, and ovaries, as well as from different host developmental stages. Transcripts for SpliTrf were detected in all developmental stages, but SpliTrf was found to be preferentially expressed in the fat body tissue. Furthermore, we analyzed SpliTrf expression in response to Spodoptera littoralis nucleopolyhedrovirus, SpliNPV, and Bacillus thuringiensis infection. Our results show that while SpliTrf expression is upregulated upon bacterial infection, it is downregulated upon baculoviral infection. We discuss the role of transferrin in iron metabolism as well as in host immune physiology.