Background: Over the years, hepatitis E virus (HEV) infection has been recognized as an important cause of acute viral hepatitis of zoonotic risk and public health importance globally. The recent HEV infection outbreaks in Nigeria and other Sub-Saharan African countries has further increased its livestock production importance, public health significance and need for serosurveillance. Methods & Materials: This study took a cross-sectional epidemiological approach to determine the seroprevalence of Hepatitis E virus infection in animals (goat, cattle and pigs) slaughtered at the Bodija municipal abattoir, the associated risk factors and evaluation of the pathological changes in the HEV seropositive animals. A total of 176 animals (120 pigs, 30 cattle and 26 goats) were sourced from the Bodija Municipal abattoir, Ibadan, Nigeria. Haematology, serum biochemistry and serological detection of the anti-HEV antibody using a multispecies bi-well ELISA kit was carried out. Liver and spleen samples were also taken for histopathological examination and lesion scoring. Results: 66 (55%) of the pigs sampled were seropositive while all the goats and cattle were seronegative. In the pig population, there was a significant difference (p < 0.05) in the seroprevalence of HEV in the different predisposing factors (age, sex, breeds and husbandry system). A higher seroprevalence was reported in the female pigs (60.27%) than in the male pigs (46.81%) while more of the pigs < 6 months (63.16%) were seropositive compared to those > 6 months (47.62%). HEV seropositivity was associated with a significant (p < 0.05) decrease in the total white blood cell (12.41 ± 5.96 × 103/ μL) and an increase in the monocyte count (0.72 ± 0.12 × 103/ μL) and the platelet count (2.23 ± 0.43 × 105/ μL) compared to the seronegative pigs. There was also a significant elevation in the hepatocellular damage and cholestatic enzymes in the seropositive pigs. There was a significantly higher frequency and severity of the post-mortem lesions in the seropositive pigs. Conclusion: This study shows the high seroprevalence of HEV infection in pigs, and importance of age, breed, sex and the husbandry system as predisposing risk factors. It also underscores the need for further HEV studies in Nigeria (to aid preparedness in the disease prevention and control) and its impact on livestock production and public health.