Objectives Critical illness in COVID-19 is attributed to an exaggerated host immune response . Since neutrophils are the major component of innate immunity, we hypothesize that the quantum of activated neutrophils in the blood may predict adverse outcome . Design In a retrospective study of 300 Omani adult patients with confirmed COVID-19, we analyzed the impact of neutrophil activation (NEUT-RI), interleukin-6 (IL-6) and the established clinical risk factors of age, diabetes, obesity and hypertension on the clinical outcome . Results Significant predictors of the need for mechanical ventilation were NEUT-RI (OR = 1.22, p <0.001), diabetes (OR = 2.56, p = 0.00846) and obesity (OR 6.55, p <0.001). For death, the significant predictors were NEUT-RI (OR = 1.14, p = 0.00432), diabetes (OR = 4.11, p = 0.00185) and age (OR = 1.04, p = 0.00896). The optimal cut-off value for NEUT-RI to predict mechanical ventilation and death was 52 FI (sensitivity 44%, specificity 88%, AUC 0.67 and 44% , 86%, AUC 0.64 respectively). Conclusion This finding supports an aberrant neutrophil response in COVID-19, likely due to uncontained viral replication, tissue hypoxia and exacerbated inflammation, introduces a novel biomarker for rapid monitoring, and opens new avenues for therapeutic strategies.