Objectives: The aim of this study was to compare the quality of sedation and recovery, and ease of venepuncture following sedation for feline blood donation using two intramuscular (IM) sedation protocols: alfaxalone/butorphanol (AB) and dexmedetomidine/butorphanol (DB). Methods: This was an experimental randomized, blinded, crossover study. Ten client-owned healthy cats were recruited to participate in the study. Cats were sedated with AB (alfaxalone 2 mg/kg and butorphanol 0.2 mg/kg) for one donation and DB (dexmedetomidine 10 mug/kg and butorphanol 0.2 mg/kg) for another. Reaction to injection, quality of sedation and quality of recovery were assessed by a blinded observer. Time to lateral recumbency, number of venepuncture attempts, time required for blood collection and time to return to sternal recumbency were recorded. Cats were monitored for evidence of gastrointestinal distress. Each donation consisted of a maximum of 53 ml whole blood drawn over 3-22 mins. Donors received 100 ml subcutaneous lactated Ringer's solution in recovery. Owners, unaware of sedation protocol, were asked to complete a questionnaire evaluating their cat's behavior following sedation. Results: IM injections were well tolerated by both treatment groups. There was no significant difference between treatment groups in sedation scores for posture ( P = 0.30) or behavior ( P = 0.06). Cats sedated with DB had significantly higher muscle relaxation scores ( P = 0.03) compared with AB. There was no significant difference between treatment groups in time to lateral recumbency ( P = 0.12), number of venepuncture attempts ( P = 0.91) and time for blood draw ( P = 0.29). There was no difference in quality of recoveries between treatment groups based on simple descriptive scores ( P = 0.18) and owner evaluation 24 h following sedation. One cat vomited following administration of DB. Conclusions and relevance: Alfaxalone is a suitable alternative to dexmedetomidine when combined with butorphanol and used as part of an IM sedation protocol for cats undergoing blood donation.