The aim of this study was to evaluate the anesthetic effects of xylazine-ketamine (XK), xylazine-tiletamine-zolazepam (XTZ) and tiletamine-zolazepam (TZ) using hematological and biochemical parameters in rabbits. A total of 18 rabbits were divided into three equal treatment groups (n = 6). The rabbits in the XK, XTZ, and TZ groups were administered xylazine (5 mg/kg) and ketamine (50 mg/kg), xylazine (5 mg/kg) and TZ (15 mg/kg), and TZ (15 mg/kg), respectively, via the intramuscular route. Following the injection, their reflexes were tested every 5 minutes. Heart rate, respiratory rate, and body temperature were determined before the injection (0 min) and at 5, 15, 30, 45, 60, 75, 90, and 120 min after injecting the anesthetic combinations. Furthermore, hematological and biochemical (alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP], bilirubin, blood urea nitrogen [BUN], and urea) analyses were also performed before, during, and after anesthesia administration. The duration of anesthesia and loss of reflexes were significantly longer in the XTZ group than in the other groups. However, in the TZ group, reflexes were remained. Respiratory rate and body temperature decreased in all the groups. Moreover, heart rate reduced only in the XK and XTZ groups, and the hematological parameters of all groups were comparable. Serum AST and ALP levels increased in the XTZ group compared to that in the XK and TZ groups, respectively. However, these increases were within the reference limits. The post-anesthesia serum BUN and urea levels significantly increased in the XTZ group (p < 0.05) compared to that in the other groups. Thus, although the XTZ combination provided satisfactory anesthetic effect in rabbits, it may be nephrotoxic. Therefore, its use for anesthesia induction in invasive renal procedures and experimental nephrotoxicity studies is not advisable.