Background: Neonatal foals are born essentially agammaglobulinemic and therefore must ingest colostrum or receive immunoglobulins to maintain health. Failure of passive transfer treatment involves administration of equine colostrum, plasma or commercial powdered colostrum (CPC). Anecdotal reports suggest a risk of anaphylaxis associated with plasma transfusion in neonates that received CPC prior to gut closure. Bovine serum albumin (BSA) in CPC may serve as a target for BSA-specific immunoglobulin E (IgE) in donor equine plasma. Objectives: To determine presence of BSA-specific IgE in samples collected post-routine vaccination in healthy horses, horses experiencing adverse vaccine reactions and commercial equine plasma. Study Design: Prospective Observational Methods: Serum was collected from 65 healthy horses at day 0, 14, 28, 90, 180, 270 and 365 post-vaccination, 26 horses after vaccine reaction at day 1, 180 or 270 post-vaccination, 4 horses not vaccinated and 10 horses from a commercial plasma donor herd. BSA-specific IgE was determined using enzyme-linked immunosorbent assay (ELISA). Results: BSA-specific IgE was not detected in non-vaccinated horses and was identified in all vaccinated horses. Younger horses demonstrated higher fold changes in post-vaccination BSA-specific IgE expression compared to older horses. No significant difference in BSA-specific IgE levels between commercial plasma donors and healthy horses was identified. No significant difference in post-vaccination anti-BSA IgE levels between reactor and healthy horses at day 180 and 270 post-vaccination were identified. Main Limitations: Small number of reactor horses at day 180 and 270 post-vaccination with most samples being collected 24 hours. There were no healthy horse samples for 24 hours post-vaccination; therefore, it was not possible to compare the two groups at this timepoint. Conclusions: Horses may express BSA specific IgE following vaccination. There may be risk of hypersensitivity type reaction when veterinarians administer commercial plasma to neonatal foals that have consumed CPC prior to gut closure.