Life history theory predicts that nutritionally costly life stages must be timed and balanced with the competing costs of self-maintenance. In birds, molt is known to be very expensive in terms of nutrient requirements due to the metabolic costs associated with producing high quality feathers quickly. The trade-offs between investments in self-maintenance and immunity are known to be important, but the relationship between molt and immunity remains unclear. Because both molt and the ability to mount an immune response are essential for survival, there is likely a trade-off wherein molt negatively impacts the ability of a bird to mount an immune response. The objective of this study was to use chickens (Gallus gallus domesticus) to clarify the impacts of molt on nutritional investment in immunity using an expensive innate immune system challenge. We used a 2×2 factorial arrangement of treatments (n = 7): 1) No molt control 2) No molt control + challenge 3) Molt and 4) Molt + challenge. To induce molt, chickens went from a long day schedule to a short-day schedule along with oral thyroxine. An injection of lipopolysaccharide (LPS) was administered three weeks after the onset of molt to initiate an acute phase response. Four hours after the LPS injection; tissue samples were collected for evaluation of cytokine expression using qPCR. Molt led to a significant increase in the size of both the spleen (p < 0.001) and the thymus (p < 0.001). Chickens undergoing molt generally had the lowest inflammatory response to LPS compared to the other treatment groups. This research clarifies the trade-off between molt and immunity and helps us understand one of the factors likely to motivate the variance in molt strategies among avian species.