Background: As cats undergo stress at the time of presentation before surgery and therefore sedation is required often. It is very difficult to choose a balanced anaesthetic protocol during the surgical intervention in the case of a cat. Therefore, the present study was undertaken to evaluate the effect of ketamine hydrochloride in combination with midazolam, dexmedetomidine and butorphanol as balanced anaesthesia on clinico-physiological, haematological, serum biochemical profile in the surgical management of cats undergoing neutering. Methods: The study was performed on 18 clinical cases of cats which were brought to the Teaching Veterinary Clinical Complex, College of Veterinary Sciences and Animal Husbandry (CVSc and AH), Central Agricultural University (CAU), Selesih, Aizawl, Mizoram for elective surgery such as neutering. Cats were randomly divided into 3 equal groups, i.e. Gr. A, Gr. B and Gr. C. Animals were premedicated with glycopyrrolate @ 0.01 mg/kg, i/m. After 10 minutes of premedication, in Gr. A ketamine hydrochloride @15 mg/kg and midazolam @ 0.5 mg/kg, in Gr. B ketamine hydrochloride @10 mg/ kg and dexmedetomidine@ 5 mcg /kg and in Gr. C ketamine hydrochloride @ 5 mg/kg, dexmedetomidine@ 5 mcg/kg and butorphanol @ 0.2 mg/kg was administered intramuscularly. Clinico-physiological and haemato-biochemical profiles were evaluated at 0 minute (baseline), then at 15, 30 and 60 minutes after administration of anaesthetic agents to evaluate their anaesthetic effect. Result: In the case of time for induction, the quality of induction, assessment of peri-operative analgesia, depth of anaesthesia and quality of recovery there was no significant difference among all three groups. In Gr. B, animals showed significantly higher duration of recumbency (DOE) and recovery. The assessment of peri-operative analgesic effect among the groups revealed that analgesia during the perioperative period appeared best in Gr. C protocol. In regards to depth of anaesthesia, ketamine hydrochloride in combination with dexmedetomidine and butorphanol group showed a better result. Rectal temperature decreased significantly (P greater than 0.05) up to 60th minutes in Gr. A, but it remained within the physiological range. Heart rate raised significantly (p less than 0.05) from the baseline (0 minutes) onwards and decreased significantly (p less than 0.05) till the end (60 minutes) of the study in Gr. C. The respiration rate was significantly (p less than 0.01) different in between time intervals for all three groups. No significant difference was observed on haemato-biochemical observation except glucose level which significantly increased after induction of anaesthesia. In conclusion, treatment with ketamine hydrochloride in combination with dexmedetomidine and butorphanol led to acceptable sedation and mild changes in clinico-physiological, haematological, serum biochemical profile in comparison to the other two groups.