Abstract Background The aim of this prospective and complete cross-over study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on EEG parameters derived from the Narcotrend® Monitor before and after nociceptive stimulation at different isoflurane MAC (minimal alveolar concentration) multiples. Seven adult European Domestic Short Hair cats were used. Each cat went through 3 experimental treatments. Group I received isoflurane, group IR received isoflurane and a constant rate infusion (CRI) of remifentanil (18 μg/kg/h IV), and group ID received isoflurane and a CRI of dexmedetomidine (3 μg/kg/h IV). The isoflurane MAC in each group was determined via supramaximal electrical stimulation. The EEG parameters were derived by a Narcotrend Monitor at specific time points before and after nociceptive stimulation at 0.75, 1.0 and 1.5 MAC. The depth of anaesthesia was also assessed by a clinical score. Results The mean MAC sparing effects in group IR and group ID were 9.8 and 55.2%, respectively. The best correlation of EEG and MAC multiples was found for the Narcotrend Index (NI) in group I (r = − 0.67). The NI was also able to differentiate between 0.75 MAC and 1.5 MAC in group IR. Spectral edge frequency had a lower correlation with MAC multiples in group I (r = − 0.62) but was able to differentiate between 0.75 MAC and 1.5 MAC in groups I and IR, and between 1.0 MAC and 1.5 MAC in group IR. Narcotrend Index, SEF 95 and MF increased significantly after nociceptive stimulation at 1.0 MAC in group I, and SEF 95 increased significantly at 0.75 MAC in group ID. The clinical score correlated closer than any of the EEG parameters with MAC in all groups, with highest correlation values in group I (r = − 0.89). Noxious stimulation led to a significant increase of the clinical score at 0.75 MAC and 1.0 MAC in group I. Conclusions The EEG parameters derived from the Narcotrend Monitor show correlation to isoflurane MAC multiples in cats, but the anaesthetic protocol and especially the addition of dexmedetomidine have great influence on the reliability. The Narcotrend Monitor can be used as an additional tool to assess anesthetic depth in cats.