BACKGROUND: Macroamylasemia is a rare condition affecting 0.5-1.5% of the population. Macroamylasemia should be suspected in a patient with a high serum alpha-amylase level without an elevation in the urine alpha-amylase level. Serum amylase binds with other serum proteins like immunoglobulins A (92%), immunoglobulins G (<
30%), and others (<
5%), forming macromolecular complexes that weigh more than 400 KDa. Nephrones are unable to secrete these macromolecules into the urine due to their large size, which causes the accumulation of these macromolecules in the serum. Patients with COVID-19 during seroconversion develop higher concentrations of SARS-CoV-2-specific immunoglobulins and different plasma proteins, which can bind with the alpha amylase molecules and cause macroamylasemia. CASE PRESENTATION: In this case report, we report about a 70-year-old hypertensive and asthmatic patient who was under inward treatment for mild COVID-19. He complained ofburning epigastric pain for one day and his elevated serum amylase level persisted months after the initial presentation. He underwent extensive investigations to exclude acute pancreatitis and other causes of high amylase levels. His amylase creatinine clearance ratio was 0.2%, his pre- polyethylene glycol(PEG) amylase concentration was 644 U/L, and his post-PEG amylase concentration was 10 U/L with a very low post-PEG recovery (1.55%). He was diagnosed with macroamylasemia.