<p>Peste des petits ruminants (PPR) vaccination can induce oxidative and physiological stress in naïve goats, highlighting the need for supportive interventions to enhance post-vaccination resilience. The present study evaluated the effect of injectable immune modulators and antioxidants on the haematological, hormonal, and redox biomarkers in Rohilkhandi goats, a local registered goat breed of Uttar Pradesh, India, during Peste des petits ruminants (PPR) vaccination. Eighteen apparently healthy goats were divided into three groups (06 each): Control – vaccinated against PPR without supplementation; T1 – vaccinated against PPR with levamisole (2.5 mg/kg BW, SC, thrice at 3-day intervals); and T2 – vaccinated against PPR with Vitamin E and Selenium (1 ml/25 kg BW, SC, twice at 7-day interval). The first dose of each supplement was administered on the day of vaccination. Serum samples were isolated before (0 days) and after vaccination at different time points (3, 7, 14, and 21 days) for haematological, and hormonal [T3 (Triiodothyronine), T4 (Thyroxine), and cortisol] profiling. In addition, five redox biomarkers—Superoxide Dismutase (SOD), Total Antioxidant Capacity (TAC), Catalase (CAT), Glutathione Peroxidase (GPX), and Total Thiol Levels (TTLs)—along with nitrosative and oxidative stress markers, nitrate (NO₃⁻, as a proxy for nitric oxide) and malondialdehyde (MDA), were also assessed. To evaluate humoral immunity, blood samples were also collected at 0, 3, 7, 14, 21, 30, 60, 90, 120, and 150 days post-vaccination (dpv). Compared to the control, the T2 group showed significantly higher total leukocyte and neutrophil counts at 3 and 7dpv, and increased lymphocyte counts at 7dpv. Antioxidant (vitamin E and selenium) and immunostimulant (levamisole) supplementation in PPR-vaccinated goats significantly modulated stress and redox responses. Cortisol levels were reduced in both supplemented groups compared to the control, indicating lower stress post-vaccination. Antioxidant-treated goats (T2) showed enhanced redox status, with significantly elevated levels of SOD, GPX, CAT, TAC, and total thiols, and reduced oxidative (MDA) and nitrosative (nitrate) stress markers compared to the control. However, antibody responses measured by percent inhibition (PI) using competitive ELISA did not differ significantly among the groups, suggesting similar levels of seroconversion across groups. These findings suggest that while primary PPR vaccination induces oxidative and nitrosative stress, antioxidant supplementation can effectively improve redox balance and stress response. Immunomodulators and antioxidants appear to support cellular immunity and physiological resilience, though they may not significantly alter humoral antibody production post-vaccination. These results underscore the potential benefit of integrating antioxidant and immunomodulatory support into PPR vaccination protocols to enhance health outcomes and disease resilience in goats.</p>