Hepatitis E is a zoonosis that can be acquired by the consumption of contaminated food or water, or via person-to-person spread. However, little is known about the transmission of hepatitis E virus (HEV) in the UK. We investigated the epidemiology of indigenous hepatitis E infection using the PHLS Farm Cohort, a sentinel group with a history of close contact with a range of domestic animals. Ten of the 413 subjects tested were positive for hepatitis E IgG antibodies (2.4%). Seroprevalence peaked in those aged 51 to 60 years (relative risk 3.3, 95% CI: 1.0-10.5). Male participants (relative risk 3.6, 95% CI: 0.6-21.2) and those from farms in the Hereford area of the United Kingdom (relative risk 2.7, 95% CI: 0.8-8.4), an area of mixed livestock farming, were more likely to have serological evidence of previous HEVs exposure, although these findings were not statistically significant. Exposure to pigs, or water from a private supply, was not identified as a significant risk factor. The results of this study suggest that UK farming populations are exposed to HEV, but the predominant route of transmission remains elusive.