The immune system protects organisms against infection, but this protection presumably comes at a cost. Here, we asked whether food restriction would compromise the ability of an organism to generate an immune response upon re-exposure to an antigen, which would represent a functional cost of immunological memory. Immunological memory is generated when B and T lymphocytes sensitive to components of pathogens (i.e., antigens) proliferate post-exposure and persist in circulation to hinder re-infection. To test the possibility that B-cell memory, the component of the immune system responsible for antibody production, is expensive to maintain, secondary antibody production against a novel protein (keyhole limpet hemocyanin, KLH) was compared between food-restricted and ad libitum fed male deer mice, Peromyscus maniculatus. To determine whether compromised secondary antibody production was solely due to elevated corticosterone independent of resource availability, some food-restricted and ad lib fed mice experienced unpredictable, chronic (2 h/day) restraint. Mice provided with 70% of their ad libitum diet 2 weeks after primary antigen challenge produced ~95% less immunoglobulin G (IgG) production against KLH after a second antigen challenge relative to mice fed ad libitum, even though all mice were fed ad libitum during the secondary antibody response period. Restraint had no effect on secondary IgG production to KLH, and corticosterone concentrations one day post food-restriction did not differ between food-restricted and ad libitum fed mice. Altogether, these data imply that secondary antibody responses secondary antibody responses and the benefits of immunological memory are energetically costly in this species.