•Withdrawal of valproate (VPA) increases the alpha peak frequency (APF) in patients with epilepsy who have a normal baseline posterior dominant frequency.•APF correlates inversely with the daily dose of VPA in the absence of overt clinical or electroencephalographic signs of encephalopathy.•No significant change in APF occurs in patients withdrawn from levetiracetam (LEV). Studies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF). We retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients’ APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level. The APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = −0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = −0.17 ± 0.18 across patients, p = 0.4072). Our results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment. Our study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.