Purpose: At the beginning of the Coronavirus disease (COVID-19) epidemic, physicians paid close attention to children with chronic diseases to prevent transmission or a severe course of infection. We aimed to measure the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) antibody levels in children with chronic gastrointestinal and liver diseases to analyze the risk factors for infection and its interaction with their primary disease. Methods: This cross-sectional study analyzed SARS-CoV-2 antibody levels in patients with gastrointestinal and liver diseases (n=141) and in healthy children (n=48) between January and February 2021. Results: During the pandemic, 10 patients (7%) and 1 child (2%) had confirmed COVID-19 infection (p=0.2). The SARS-CoV-2 antibody test was positive in 36 patients (25.5%) and 11 children (22.9%) (p=0.7). SARS-CoV-2 antibody positivity was found in 20.4%, 26.6%, 33.3%, and 33.3% of patients with chronic liver diseases, chronic gastrointestinal tract diseases, cystic fibrosis, and liver transplantation recipients, respectively (p>0.05, patients vs. healthy children). Risk factors for SARS-CoV-2 antibody positivity were COVID-19-related symptoms (47.2% vs. 14.2%, p=0.00004) and close contact with SARS-CoV-2 polymerase chain reaction-positive patients (69.4% vs. 9%, p<0.00001). The use, number, and type of immunosuppressants and primary diagnosis were not associated with SARS-CoV-2 antibody positivity. The frequency of disease activation/flare was not significant in patients with (8.3%) or without (14.2%) antibody positivity (p=0.35). Conclusion SARS-CoV-2 antibodies in children with chronic gastrointestinal and liver diseases are similar to that in healthy children. Close follow-up is important to understand the long-term effects of past COVID-19 infection in these children.