Amphibians appear to require higher doses of sedatives than other animals, but studies evaluating doses and its impacts are limited. The goals of this project were to 1) determine the effective dose 50 (ED50) of IM dexmedetomidine- and midazolam-alone, 2) evaluate the cardiopulmonary effects of IM dexmedetomidine-midazolam at ED50 (DexMidED50), and 3) evaluate the short-term impact (up to 2 hours) on activity following reversal with flumazenil in Sonoran Desert toads (Incilius alvarius). A total of 21 toads were available for ED50 study. Using a clinically applicable sedation score, ED50 of dexmedetomidine- and midazolam-alone were calculated using the Dixon’s Up-and-Down method as 0.5 and 5 mg/kg, respectively. Subsequently, the cardiopulmonary parameters (DexMidED50 [n=6] or positive control [saline at equal volume and same handling as DexMidED50, n=6]) were evaluated every 5 min for 30 min. Statistically significant bradycardia and bradypnea was noted in the DexMidED50, vs. positive control and/or baseline. DexMidED50 was reversed with atipamezole (5 mg/kg IM) and flumazenil (0.4 mg/kg SC), and positive control received equal volume of saline. Both groups plus a negative control (no handling or injections, n=6) were monitored using a Noldus EthoVision XTTM for 2 hours. DexMidED50 was not different from positive control but it was significantly slower, traveled shorter distances, and spent less time moving in comparison to the negative control. High doses of dexmedetomidine and midazolam are needed to induce clinical sedation and these produce significant cardiopulmonary side-effects which may be dangerous in non-healthy animals. Activity is affected for at least 2 hours post-reversal.