Background: Anaesthetic agents are gaining popularity in the world of diagnostic and surgical procedures, but little is known about their combined biochemical action. This paper compared the impacts of ketamine and lidocaine given alone and in combination with each other on serum electrolytes and plasma proteins in male Wistar rats. Methodology: 35 male Wistar rats randomized to five groups (n=6): control, lidocaine, lidocaine with adrenaline, ketamine, and ketamine with lidocaine. The samples of blood were taken out at the end of the experimental period by cardiac puncture. Automated biochemical methods were done to determine serum electrolytes (sodium, potassium, chloride, calcium), plasma proteins (total protein, albumin, globulin, fibrinogen). The data were presented in the form of mean ± SEM and compared by a one-way ANOVA with p=0.05. Results: Lidocaine adrenaline and ketamine had a significant impact on serum potassium levels in comparison with the control group, making it prone to hyperkalemia. Ketamine too raised serum calcium, total and globulin and fibrinogen levels significantly but albumin was not altered significantly. The level of Na+ and Cl were found to have small, non significant differences among the groups. Discussion: The observed case of hyperkalemia after administration of ketamine and lidocaine combined with adrenaline indicates the disruption of the ion transportation process on the membrane, and causes the concern of cardiovascular issues, particularly in patients with an underlying electrolyte disturbance, or with medications that inhibit the ion transport. The rise in the levels of calcium and globulin after the exposure of ketamine also points to the possible metabolic and inflammatory regulation. Conclusion: Ketamine and lidocaine combined and administered separately produce a significant change in serum potassium, calcium, and plasma protein. The use of these agents should hence be cautious especially among those individuals who are in