Ictal respiratory dysfunction occurs in patients with epilepsy and may contribute to sudden unexplained death in epilepsy (SUDEP). Fluoxetine reverses respiratory arrest in a mouse model of epilepsy, suggesting that selective serotonin reuptake inhibitors (SSRIs) may reduce ictal respiratory dysfunction. Video–electroencephalography (EEG) and pulse oximetry data from 496 seizures in 73 consecutive patients with partial epilepsy was reviewed, including 87 seizures in 16 patients taking SSRIs (SSRI+) and 409 seizures in 57 patients not taking SSRIs (SSRI)). The proportion of ictal-related oxygen desaturation <85% with partial seizures without secondary convulsions in SSRI+ patients was reduced relative to SSRI) patients (p = 0.011). There was no statistically significant difference in ictal oxygen desaturation for secondarily generalized convulsions. SSRIs are associated with reduced likelihood of ictal oxygen desaturation in patients with partial seizures.