Introduction Electroencephalography (EEG) recording and drug administration is commonly used for neurological experiments in rats, but is typically cumbersome due the use of multiple lines. We have developed a unique system, which allows long-term simultaneous video-electroencephalography recording, drug infusion and blood sampling in rats. Methods The vEEG/drug infusion system was designed and tested on two contrasting animal models of epilepsy. Animals were implanted with EEG-electrodes and a jugular vein cannula fixed in a head cap, avoiding an additional cable for tethering. In an acute infusion study ( n = 16), repeated blood samples were taken after i.v. bolus injection of valproate. In a subset of these rats ( n = 10), paired blood samples were removed from the jugular vein and the heart after valproate administration. In a chronic infusion study ( n = 38), heparinised (4 IU/h) saline or valproate (42 mg/kg/h) was infused continuously for up to 17 days. Results In the acute study, repeated blood samples showed a decrease in plasma valproate levels over time following bolus injection. In the chronic study, high quality continuous EEG was achieved and 79% of animals were successfully infused throughout the planned infusion period (13–17 days), with 66% of projected blood samples able to be taken during the infusion. There was a high correlation between the jugular vein and cardiac plasma levels of valproate (Spearman test, r = 0.69; p < 0.05). Conclusion This system is ideal for pharmacokinetic/dynamic studies and long-term drug infusion where simultaneous EEG and/or frequent blood sampling are desired.