BACKGROUND: Coronavirus disease 2019 (COVID-19) started in Asia, and Iran was one of its first epicenters. AIM: To study the gastrointestinal (GI) symptoms and comorbidities associated with this pandemic in four different regions of Iran. METHODS: We analyzed data from severe acute respiratory syndrome coronavirus 2 positive patients evaluated at four hospitals of Iran (n = 91), including South (Shiraz), Southeast (Dezful), Rasht (North), and Northwest (Mashhad) between April and September 2020. Demographics, comorbidities and clinical findings including GI symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities, and mortality were performed. RESULTS: The average age of COVID-19 patients was 51.1 years, and 56% were male. Mortality rate was 17%. Cough with 84.6%, shortness of breath with 71.4%, fever with 52.7%, and loss of appetite with 43.9% were the main symptoms. Overall cardiac disease was the most common comorbidity with an average of 28.5% followed by hypertension (28.5%) and diabetes (25.2%). The highest comorbidity in North (Rasht) was diabetes (30%) and in South (Dezful) hypertension (37%). Shiraz leads cardiac disease with 43.4%. The most reported GI symptoms included nausea, diarrhea, vomiting, and abdominal pain, with 42.8%, 31.8%, 26.8%, and 12% prevalence, respectively. In addition, albumin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were elevated in 26.3%. CONCLUSION: Our results show hypertension and diabetes as the most common comorbidities, but their distribution was different in COVID-19 patients in the four studied regions of Iran. Nausea, diarrhea, and elevated liver enzymes were the most common GI symptoms. There was also a high mortality rate that was associated with high infection rates in Iran at the beginning of the pandemic.