Background: Lidocaine and ketamine are anaesthetic agents usually used in clinical practice to manage pain and as preoperative agents. In addition to this, anaesthetic medications can affect other haematological parameters, such as erythrocyte sedimentation rate (ESR) and osmotic fragility. Changes in these parameters may be a sign of the risk of anaemia, inflammation, or oxidative injury after anaesthetic exposure. The literature on these effects is however inconsistent and there is limited comparative data on lidocaine and ketamine. Therefore, the aim of this study was to compare and contrast the influence of these two anaesthetic agents on ESR and erythrocyte osmotic fragility in male Wistar rats. Methodology: A total of 35 male wistar rats were used for this study after undergoing acclimatization for one week. The animals’ blood samples were collected and analysed using appropriate techniques. One way ANOVA was adopted as the statistical analysis method for this study and data were reported as mean ± SEM, where the level of significance was set at p < 0.05. Results and Discussion: There were no statistically significant differences in both the treatment and control groups when it came to ESR and osmotic fragility and the same meaning that lidocaine and ketamine did not impact the erythrocyte membrane stability or the inflammatory condition. Conclusion: The results concluded that the lidocaine and ketamine are safe in Hb parameters, and can be further used in the anaesthetic practice without causing any erythrocyte injury or inflammation.