An important gap of knowledge exists regarding the public interest in hepato-pancreato-biliary (HPB) diseases during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the public interest in HPB diseases in the COVID-19 era. In this infodemiology study, we performed a comparative analysis of Google search volume of HPB terms in 2020-2021 and compared it to a similar time frame (2016-2019) in 3 periods to assess how trends in patient seeking behavior of HPB terms changed during the course of the pandemic in the USA and worldwide. Our analysis showed a substantial decrease in search volume of HPB diseases and procedure terms early in the pandemic. However, search volumes appeared to revert back to pre-pandemic years closer to the 1-year mark in USA and worldwide. Patients may have initially neglected HPB-related issues during the early phase of the COVID-19 pandemic, which could lead to worse outcomes. While HPB-related terms reverted closer to pre-pandemic levels later in the pandemic, further research is needed to assess the long-term impacts.