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Objectives: The aims of this study were to evaluate and compare the effects that dexmedetomidine and methadone, either alone or in combination, have on the ocular variables of healthy adult cats when administered intramuscularly, as well as their reversal with atipamezole., Methods: A randomized crossover blinded study of 10 healthy cats was used to assess the effect of 0.2 mg/kg methadone (MET), 7.5 μg/kg dexmedetomidine (D7), 10 μg/kg dexmedetomidine (D10), 7.5 μg/kg dexmedetomidine and 0.2 mg/kg methadone (DM7) and 10 μg/kg dexmedetomidine and 0.2 mg/kg methadone (DM10) on intraocular pressure (IOP), tear production and pupil diameter (PD). The animals were evaluated for 30 mins. Afterwards, atipamezole was administered and ocular variables were evaluated for 30 mins., Results: D10, DM7 and DM10 significantly decreased mean IOP but MET or D7 did not. Tear production decreased significantly in all treatments, corresponding to 18%, 59%, 63%, 86% and 98% in MET, D7, D10, DM7 and DM10, respectively. PD increased in all treatments, but MET showed the highest PD. Thirty minutes after atipamezole (RT30), IOP returned to baseline with no difference between groups, and there was a significant increase in tear production, but the means were still different from baseline., Conclusions and Relevance: Dexmedetomidine decreases IOP and tear production but increases PD in healthy cats. Atipamezole can partly reverse those alterations. Low-dose dexmedetomidine (7.5 µg/kg) promotes sedation without changing the IOP. All protocols significantly decrease tear production, and Schirmer tear test after sedation is not representative of non-sedated values. Methadone induces quick onset mydriasis without changing the IOP.