BACKGROUND AND AIMS: It is unclear to what degree post-COVID-19 gastrointestinal (GI) symptoms are caused by the SARS-CoV-2 virus vs psychological factors related to the stress of the pandemic. To evaluate this, we compared rates of long-term GI and mental health symptoms in patients testing positive vs negative for SARS-CoV-2. METHODS: Adults presenting for SARS-CoV-2 testing from April to November 2020 were prospectively enrolled in a longitudinal cohort. Six to 12 months later, the presence and severity of current GI and mental health symptoms were assessed on a 5-point Likert scale. A multivariable logistic regression model was used to estimate the odds of a positive COVID test for predicting GI symptoms, stratified by sadness/anxiety. RESULTS: 749 COVID-positive and 107 COVID-negative patients completed the survey. The prevalence of at least one GI symptom was higher in patients with COVID-19 (29 vs 18%,  = .01). However, after stratifying by sadness/anxiety, differences in GI symptoms according to COVID status were no longer significant. On multivariable analysis, the adjusted odds ratio for GI symptoms was 8.26 (95% CI 4.04-16.9) for positive COVID sadness/anxiety, 8.74 (95% CI 2.63-29.0) for negative COVID sadness/anxiety, and 1.16 (95% CI 0.57-2.39) for positive COVID sadness/anxiety, compared to a reference group of negative COVID sadness/anxiety. CONCLUSION: After accounting for sadness and anxiety, there was no association between COVID-19 and the development of long-term GI symptoms. Post-COVID GI symptoms may be mediated bidirectionally through coexisting anxiety and depression, similar to disorders of gut-brain interaction.