Background:The COVID-19 pandemic has presented a major challenge in critical care, especially in identifying patients at high risk for complications and poor outcomes. Objective:Given the pressing need to identify biomarkers that predict disease severity and outcomes, this study evaluates the association between D-dimer levels and the severity of COVID-19 infection in intensive care unit (ICU) patients, providing insights into its potential as a prognostic marker. Patients and methods:A prospective cohort of 120 COVID-19 patients was studied at Menoufia University hospitals' ICU. D-dimer levels, measured upon admission, were analyzed alongside disease progression, clinical scores, Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), complications, ICU length of stay, and mortality. Results: Demonstrated a significant positive correlation between elevated D-dimer levels and increased disease severity, with critically ill patients exhibiting markedly higher levels. Elevated D-dimer was associated with a greater incidence of complications, including deep vein thrombosis, pulmonary embolism, and multi-organ dysfunction, as well as a longer ICU stay and higher mortality. ROC analysis identified a D-dimer cutoff of 2505.4 ng/mL, yielding 74.2% sensitivity and 98.3% specificity for predicting mortality. Conclusion:D-dimer serves as a valuable, prognostic biomarker for risk stratification and identifying patients likely to experience severe outcomes. D-dimer monitoring is recommended to improve clinical outcomes in critically ill COVID-19 patients by enabling early intervention, targeted treatment and resource allocation.