Background & objective: Several studies have been conducted around the world on the impact of COVID-19 on people with diabetes mellitus (DM). Any acute illness can cause stress and increased inflammatory reactions, which increase sympathetic outflow and produce catecholamines, growth hormones, cortisol, and cytokines, all of which raise the risk and severity of complications from diabetes. Diabetes is a significant risk factor for the severity of COVID-19. We conducted this study to identify whether severe COVID-19 infection has any effect on the biomarkers, including fasting blood sugar (FBS), HbA1C, FA, INS, C-Pep, in individuals with DM. Methodology: This study was simultaneously conducted at Department of Chemistry and Biochemistry, College of Medicine of Al-Nahrain University, and Department of Medicine of Mustansiriyah University College of Medicine, Baghdad, Iraq. During the months of February and March 2022, 50 COVID-19 patients with diabetes and 50 COVID-19 patients without diabetes were included in the study. The control group included 100 healthy, sexually identical people (age 50-80), collected under the supervision of the second supervisor from relatives and students of Mustansiriyah University, College of Medicine. Venous blood samples of 5 mL were taken from all participants and subjected to laboratory tests to detect the levels of the biomarkers. Results: Average FBS level in DM patients was 304.9 mg/dL, (range 132-545.9 mg/dL), which was remarkably higher than in non-DM patient groups (193.3 mg/dL), range (of 66.2–458). The DM patients' group had a significantly higher concentration of HbA1C (median = 6.70 mg/dL, range 5.2-8.1) than the non-DM patient group (median = 5.8, range 4.2–7.6) with a significant difference. Although The group of DM patients had significantly greater FA concentrations than the group of non-DM patients. In contrast, the median and range for insulin and c-peptide Displays non-significant differences for covid-19 patients (DM and non-DM), but it's significant with a control group. Conclusion: According to this study, COVID-19 patients with diabetes had greater biochemical indicator levels than non-diabetic people. Pre- and postprandial hyperglycemia and diabetic ketoacidosis were more common in COVID-19 DM patients than in non-infected DM patients. We found that COVID-19 increased the severity risk for T2DM patients and glucose level is raised and progresses in a vicious cycle exacerbated by insulin resistance (IR) and decreased pancreatic b-cell function. Keywords: COVID-19, Diabetes mellitus, FBS, HbA1C, FA, INS, C-Pep Citation: Yones MS, Al-Wasiti E, Al Qaseer AH, Al-Rubaiawi HK. The effect of severe COVID-19 infection on biochemical markers (FBS, HbA1C, FA, INS, C-Pep) in diabetic patients. Anaesth. pain intensive care 2024;28(5):804−808; DOI: 10.35975/apic.v28i5.2553 Received: June 01, 2024; Reviewed: June 19, 2024; Accepted: June 19, 2024