The African rock python is a cosmopolitan snake in Nigeria widely kept as a zoo animal and also in recreational facilities. There is need for chemical immobilisation of this animal species for managemental, diagnostic and therapeutic procedures. A mixture of xylazine and ketamine (XK) was compared with the administration of a mixture of xylazine and normal saline solution (XS) in six captive African rock pythons in 2 trials with reference to onset and duration of anaesthesia. Changes in the heart rate (HR), respiratory rate (RR) and rectal temperature (RT) as well as selected biochemical parameters were recorded. Although there were no statistically significant (P>0.05) differences in HR and RR values between XK and XS treatments, significant (P<0.05) differences were recorded for RT. Nonetheless, the significant differences were of no clinical importance. It was therefore recommended to safely immobilise an African rock python using XK for a procedure lasting over 1 hour with minimal cardiopulmonary and plasma enzymatic effect. To the knowledge of the authors, this is the first study assessing the anaesthetic efficacy and safety in African Rock pythons.