OBJECTIVE: To describe immune responses following administration of experimental Salmonella Dublin siderophore receptor protein (SRP) vaccines in Holstein heifer calves with adequate passive antibody transfer. METHODS: Calves were randomly assigned to receive placebo, vaccination with S Dublin SRP in adjuvant A, or vaccination with S Dublin SRP in adjuvant B at 7 ± 3 days of age and 3 weeks later. Before each vaccination, 4 and 8 days after the second vaccination (postvaccination), and 61 to 91 days postvaccination, S Dublin antibody titers were measured. Blood mononuclear cells isolated from blood collected 4 and 8 days postvaccination were stimulated with S Dublin SRP antigen (1 or 5 µg/mL) or positive or negative controls, then analyzed to quantify S Dublin SRP-responsive cells. Cultures of blood mononuclear cells were similarly stimulated to quantify interferon-γ (IFN-γ)-producing and IL-17-producing cells. The trial spanned September 4, 2022, through January 15, 2023. RESULTS: 78 calves were enrolled. Vaccinates had significantly higher IFN-γ-producing cells and IFN-γ and IL-17 concentrations at 4 and 8 days postvaccination, except IFN-γ concentration at day 4 after stimulation with 1 µg/mL. Vaccinates also had higher S Dublin titers at 8 and 61 to 90 days postvaccination. No differences in health events were noted. CONCLUSIONS: Vaccination can induce S Dublin SRP-specific humoral and cellular immune responses in Holstein heifer calves. CLINICAL RELEVANCE: Vaccination with SRP vaccines resulted in immune responses that may help mitigate S Dublin infection. Further research is needed to determine whether vaccination will be protective against S Dublin challenge.