Background: Co-administration of anesthetic adjuvants as continuous rate infusion (CRI) can be controlled and hence is considered safer, as it can reduce the cardiopulmonary alterations in horses and is also adaptable in field conditions. Hence this study was planned to evaluate the effect of CRI of dexmedetomidine, ketamine, butorphanol and midazolam during thiopentone TIVA in horses. Methods: Thirty horses were randomly divided into five groups S, D, K, B and M having six animals in each. Premedication was done with Xylazine (1 mg/kg) and butorphanol (0.05 mg/kg) intravenously. Ketamine (2 mg/kg) and midazolam (0.2 mg/kg) were used IV for induction. CRI of normal saline alone, dexmedetomidine @ 2 µg/kg/hr., butorphanol @ 0.2 mg/kg/hr., midazolam @ 0.2 mg/kg/hr. and ketamine @ 2 mg/kg/hr. were administered in groups S, D, B, M and K, respectively. Thiopentone sodium (5%) was given as a fast intravenous bolus whenever required to provide adequate anesthesia. Depth of anesthesia was evaluated on the based on clinical, haemato-biochemical, hemodynamic and endocrine variables. Result: First head lift, sternal recumbency time, standing time and quality of recovery showed no significant difference between the groups. Heart rate, RR, RT, SBP, DBP, CVP and MAP, BUN, creatinine, ALT, AST, cortisol, ACTH and ghrelin did not show significant variation among groups. Hb, PCV, TLC, TEC and neutrophil found significantly decreased and blood glucose remained significantly higher than the baseline value in all groups post induction. CRI of ketamine produced a better quality of recovery and thiopentone sparing effect and was found suitable for moderating stress response to anesthesia, inflammation and metabolic changes in horses administered with TIVA.