Sea lice (Lepeophtheirus salmonis) are the most economically important ectoparasites affecting Atlantic salmon (Salmo salar) culture worldwide. In recent years the efficacy of historically successful treatments has been on the decline. As such, a new management strategy for controlling lice infections is a high priority for the salmon farming industry. In this study, we tested the ability of three orally administered immunostimulants to decrease the number of lice successfully infecting Atlantic salmon post-smolts. It was found that the β-glucan (ProVale) fed group actually maintained more sea lice than did the control group (24% increase). However, both the CpG ODN (31–46%) and AllBrew NuPro (11–31%) fed groups showed decreased infection levels when compared to the control group. Histopathological and differential gene expression analyses indicate that localized and systemic inflammatory mechanisms may be transiently altered by these immunostimulatory feeds and may result in increased host resistance to sea lice.