© 2021 Informa UK Limited, trading as Taylor & Francis Group.Aim: Epilepsy is one of the most common neurological diseases. Dexketoprofen (DEX) is a nonselective nonsteroidal anti-inflammatory drug that is used as an analgesic. The present study aimed to assess the efficiency of DEX on WAG/Rij rats by electrophysiologically and behaviorally. Material and Methods: Twenty-eight male WAG/Rij rats were used. The effects of acute treatment with DEX (5, 25, and 50 mg/kg, i.p) on absence-like seizures, and related psychiatric comorbidity were assessed. The ECoG recording was taken for 180 min before and after drug injection. After drug injection and EcoG recording, anxiety-depression-like behavior was tested with the open field test for 5 min. Results: The 5 mg/kg DEX significantly reduced the number and duration of SWDs percentage (p < 0.05) between 120 and 180 min, but 25 and 50 mg/kg DEX significantly increased the number and duration of SWDs percentage between 0 and 30 min (p < 0.05), and after 30 min the increase stopped (p > 0.05). And also, the 5 mg/kg DEX decreased the number and duration of SWDs percentage (p < 0.05) for 180 min (p < 0.05), but 25 and 50 mg/kg DEX administration did not alter (p > 0.05). The 5, 25, and 50 mg/kg doses of DEX significantly increased the duration of grooming (p < 0.05) but did not change the number of squares crossed (p > 0.05). Conclusion: Low dose DEX reduced absence-like seizures, but care should be taken when using high doses in absence epilepsy. Also, it may be beneficial for painful diseases accompanied by anxiety-depression.