Several immunostimulatory feed additives have shown the ability to induce protective responses in Atlantic salmon to infection with Lepeophtheirus salmonis. However, even the most encouraging results rarely surpass a 50% protective index in the host. That fact coupled with the well-documented limitations of single-therapy strategies in the effective management of parasitic infections generally make it imperative to identify therapies that can be combined in an integrated pest management approach for sea lice. With this in mind, we hypothesized that immunostimulatory feeds could enhance the protection provided by SLICE® emamectin benzoate (EMB). To test this hypothesis, Atlantic salmon were fed one of two different immunostimulatory feeds (CpG ODN or Aquate®) for c. 7 weeks, challenged with L. salmonis copepodids early within that immunostimulatory feed period and then placed on a triple-dose (150 μg kg−1) feed of SLICE® for 1 week following the completion of the immunostimulatory feeding period. CpG ODN (2 mg kg−1) and the commercial yeast extract (Aquate® 0.2%) inclusion in feeds were able to successfully induce inflammatory gene expression (interleukin-1β) in the head kidneys of infected fish at 13 and 26 days post-exposure (DPE), and 13 DPE, respectively. Lice burdens were lower on fish fed CpG ODN (18%) or Aquate® (19%) diets; however, due to variability, these were not statistically significant over time. Despite no statistically significant reductions in lice numbers, by 33 DPE fish on immunostimulatory feeds had significantly reduced cortisol levels when compared to infected fish on control diet. Cortisol levels in fish receiving an immunostimulatory diet were no different from initial baseline levels prior to infection, whereas the levels in control diet fish were significantly elevated from all other time points. Despite the positive effects on infection of fish fed immunostimulatory feeds, no synergism was observed with follow-up treatment with SLICE®. In fact, highest survival of lice was observed in fish with prior immunostimulation.