Objectives. The aim of the study is to compare the sedative, cardiorespiratory, echocardiographic, and blood gas effects of dexmedetomidine and methadone associated or not with midazolam for restraint chemistry in cats. Methods. Eighteen healthy young cats (4.06 ± 0.48 kg) were randomly sedated with two protocols, through the intramuscular route: dexmedetomidine (5 µg.kg−1), methadone (0.3 mg. kg−1) and midazolam (0.3 mg. kg−1) (DMTM, n = 9), or dexmedetomidine (7.5 µg.kg−1) and methadone (0.3 mg. kg−1) (DMT, n = 9). The cardiorespiratory parameters were measured at baseline, 5 and 10 minutes after pharmacological latency. The sedation, analgesia, and muscle relaxation scores were assessed before and 5 minutes after pharmacological latency, while arterial blood gas analysis and echocardiography were assessed before and after 10 or 15 minutes, respectively. Results. There was no difference between the protocols regarding the cardiorespiratory, blood gas, and echocardiographic parameters used. The scores for sedation, analgesia, and muscle relaxation also did not differ between the protocols, with the degree of sedation, analgesia, and myorelaxation considered satisfactory in both groups. A significant decrease in heart rate (HR) was observed after administration of the sedative protocols, reaching a maximum reduction at T10 (46% and 53% reduction in the DMT and DMTM groups, respectively). The reduction in HR had an impact on echocardiographic parameters such as CO, which decreased 53% and 56% in the DMT and DMTM groups, respectively. There was a significant reduction in PaO2, SaO2, ejection fraction, and fractional shortening in both protocols. SpO2 decreased significantly after 5 minutes of sedation in the DMT group, but with a minimum mean SpO2 of 92% in T5. The respiratory rate decreased significantly at 5 and 10 minutes in the DMTM group, while PaCO2 increased in both groups, indicating respiratory depression caused by the drugs. Conclusions and Relevance. The study pointed out that both sedative protocols can be recommended for clinical sedation of young and healthy cats in the doses used. However, both protocols resulted in cardiorespiratory depression in cats and also the particularities of the animals should be evaluated regarding reducing cardiac output by more than 50%.