Abstract Objective—To determine sedative and cardiorespiratory effects of dexmedetomidine alone and in combination with butorphanol or ketamine in cats. Design—Randomized crossover study. Animals—6 healthy adult cats. Procedures—Cats were given dexmedetomidine alone (10 μg/kg [4.5 mg/lb], IM), a combination of dexmedetomidine (10 μg/kg, IM) and butorphanol (0.2 mg/kg [0.09 mg/lb], IM), or a combination of dexmedetomidine (10 μg/kg, IM) and ketamine (5 mg/kg [2.3 mg/lb], IM). Treatments were administered in random order, with ≥ 1 week between treatments. Physiologic variables were assessed before and after drug administration. Time to lateral recumbency, duration of lateral recumbency, time to sternal recumbency, time to recovery from sedation, and subjective evaluation of sedation, muscle relaxation, and auditory response were assessed. Results—Each treatment resulted in adequate sedation; time to lateral recumbency, duration of lateral recumbency, and time to recovery from sedation were similar among treatments. Time to sternal recumbency was significantly greater after administration of dexmedetomidine-ketamine. Heart rate decreased significantly after each treatment; however, the decrease was more pronounced after administration of dexmedetomidine-butorphanol, compared with that following the other treatments. Systolic and diastolic blood pressure measurements decreased significantly from baseline with all treatments; 50 minutes after drug administration, mean blood pressure differed significantly from baseline only when cats received dexmedetomidine and butorphanol. Conclusions and Clinical Relevance—Results suggested that in cats, administration of dexmedetomidine combined with butorphanol or ketamine resulted in more adequate sedation, without clinically important cardiovascular effects, than was achieved with dexmedetomidine alone. (J Am Vet Med Assoc 2003;222:37–41)