Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue that affects performance; however, little information is available pertaining to its effects on immunity. Recently, it has been shown that supplemental CP can improve performance in weaned steers postvaccination. Thus, the objective of this study was to evaluate the effect of supplemental CP on innate and adaptive immune responses in stocker steers chronically exposed to ergovaline. Angus steers (n = 12 pens; 3 steers/pen) were stratified by weight and assigned to a 2 × 2 factorial arrangement to examine crude protein levels of supplement (14% or 18%) and ergovaline exposure (0 or 185 μg ergovaline/kg BW/d via ground endophyte-free (EF) or endophyte-infected (EI) tall fescue seed, respectively) on immune response. Consumption of low to moderate concentration of ergovaline from EI tall fescue seed was sufficient to induce mild symptoms associated with fescue toxicosis. Blood samples were collected at day 0, 42, and 56 to evaluate infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea virus (BVDV) type 1b titers following vaccine challenge. Additionally, serum cytokine concentrations were evaluated using Quantibody Bovine Cytokine Arrays on day 0, 28, and 42. Data were analyzed using PROC MIXED of SAS with repeated measures. Regardless of treatment, no differences were observed in IBR and BVDV-1b seroconversion following vaccine challenge (P > 0.05). Regardless of crude protein concentration, EI steers had greater concentrations of proinflammatory cytokines (TNF-α, IFN-γ, IL-1α), chemokines (CCL2, CCL4, MIG), anti-inflammatory cytokines (IL-2, -13, -15, -21), and various growth factors (FGF-1, IGF-1, VEGF-A) when compared to EF steers (P < 0.05). Furthermore, VEGF-A and IGF-1 concentrations were greater in EI-14 steers on day 28 compared to EI-18, EF-14, and EF-18 steers (P < 0.05), however, this difference was not observed on day 0 or 42 (P > 0.05). Based on these data, steers exposed to ergovaline have an increase in pro- and anti-inflammatory cytokines and supplemental CP had minimal impact to mitigate this response. However, in the current study, exposure to ergovaline had little to no effect on adaptive immunity and response to vaccination. Together, chronic exposure to ergovaline results in a hyperactive innate immune response, which may lead to an immuno-compromised animal.