Diabetes mellitus (DM) is a risk factor for severe coronavirus disease 2019 (COVID-19) and even death. This study assessed the blood levels of immune-inflammatory and other biomarkers in severe COVID-19 diabetic patients and identified possible predictive biomarkers for disease severity. The cross-sectional study was conducted in a tertiary hospital in Gaza from 15 February 2022 to 15 July 2022. The study patients were in three Groups (each group 14 patients): ICU severe COVID-19 diabetic patients (Group 1), non-hospitalized non-diabetic patients with mild/moderate COVID-19 (Group 2) and non-COVID-19 diabetic patients (Group 3). The evaluated blood biomarkers and statistically analyzed were CRP, LDH, PCT, Ang-II, IL-6, ferritin, ESR (immune-inflammatory biomarkers), D-dimer (coagulative biomarker), CK-MB and cTn I (cardiac biomarkers), AST, ALT (liver biomarkers), HbA1c, RBC, HGB, WBC and LYM (hematologic biomarkers). ICU diabetic patients (Group 1) had the highest average age. Group 1 patients had significantly more elevated CRP, LDH, PCT, AngII, Ferritin, IL-6 and ESR, D-dimer and CK-MB levels than the other two groups at P< 0.05. Group 2 patients showed higher levels than Group 3 patients. Haematological biomarkers, except WBC, were higher among patients in Group 3 than in the other two groups. There was no significant difference between the three patient groups regarding AST and ALT levels. The study results showed a high association between LDH, PCT, Ang II, ferritin, IL-6, CK-MB, cTn I, D-dimer and LYM levels and the severity of COVID-19 in diabetic patients. These findings support the notion that DM can lead to the rapid progression of COVID-19 and make it more prone to an inflammatory cytokine storm and cardiac and coagulation problems, which could lead to various organ failures and a bad prognosis of COVID-19.