Neospora caninum is an apicomplexan parasite that in cattle assumes particular importance, as it is responsible for abortions reported worldwide. Leptin is an adipokine mainly secreted by adipocytes, which beside its role in maintaining metabolic homeostasis also has important effects in both innate and adaptive immunity. In previous work, we showed that mice chronically infected with N. caninum had elevated serum leptin levels. Here, we sought to assess whether acute infection with N. caninum infection influenced the production of this adipokine as well as leptin receptor mRNA levels. Our results show that acute infection with N. caninum led to decreased leptin serum levels and mRNA expression in adipose tissue. A decrease in leptin receptor transcript variant 1 mRNA (long isoform) and leptin receptor transcript variant 3 mRNA (one of the short isoforms) expression was also observed. An increase in the number of cells staining positive for leptin in the liver of infected mice was observed, although this increase was less marked in Interleukin (IL)-12/IL-23 p40-deficient mice. Overall, our results show that N. caninum infection also influences leptin production during acute infection.