OBJECTIVES: To examine the association between work productivity loss and/or activity impairment and epilepsy seizure frequency among people with epilepsy (PWE) from the caregiver’s perspective. METHODS: A cross-sectional survey of 500 caregivers of PWE, recruited through the Epilepsy Foundation and Light Speed Research panels, was administered. The IRB-approved survey assessed patient and caregiver demographic characteristics, aspects of epilepsy management and impact, seizure frequency, epilepsy treatments, and work productivity loss and activity impairment via the Work Productivity and Activity Impairment (WPAI) questionnaire. Generalized linear regression models were used to examine the relationship between indirect economic outcomes and seizure frequency, while controlling for caregiver and patient characteristics. RESULTS: Among the 500 caregiver respondents, 80.0% were female with an average age of 44.3 years (SD=13.0). Of these, 70.8% were married and 56.4% reported currently employed. Since becoming a caregiver, 38.6% of caregivers reported a recent change in employment status, 22.8% of whom said this was a result of caregiving responsibilities. Furthermore, 8.8% of caregivers reported being the primary wage earner of the household prior to becoming a caregiver, but who are now no longer are employed. Among the employed, caregivers reported missing on average 5.0 (SD=11.6) hours of work in the past seven days due to caregiving, resulting in 12.4% absenteeism from work. The average overall work impairment was 37.3%, and for all caregivers the average amount of activity impairment was 40.0%. After adjustments, significant increases were observed in caregiver presenteeism (p=0.008), overall work impairment (p=0.008) and activity impairment (p<0.001) as a function of seizure frequency. CONCLUSIONS: Greater epilepsy seizure frequency was associated with increased work-related and activity-related impairment, potentially resulting in increased indirect costs. Due to the chronic nature of the disease, for those who are caregivers of children with epilepsy, this loss in productivity has the potential to last for many decades.