About a quarter of COVID-19 patients develop acute kidney injury (AKI), worsening prognosis and increasing mortality. Severe COVID-19 often triggers a hyperactive immune response, influencing disease outcomes. This study examined the correlation between kidney injury biomarkers, inflammatory mediators, and mortality in COVID-19 patients. Blood samples from 390 COVID-19 patients were collected at admission and before the outcome. Serum Cystatin C (CysC), albumin, and plasma NGAL were measured via nephelometry, while inflammatory mediators (IL-4, IL-6, IL-10, IL-15, IFN-γ, TNF-α, and IL-1β) were assessed by ELISA. Most patients were male, with hypertension and diabetes as common comorbidities, and a high ICU admission rate. Lower albumin and elevated CysC and NGAL were linked to mortality. Increased inflammatory mediators correlated with lower albumin and higher CysC and NGAL, reinforcing the connection between systemic inflammation and kidney dysfunction. Elevated cytokines and kidney injury biomarkers, including NGAL, CysC, and low albumin, are strongly associated with higher mortality in COVID-19 patients. These findings highlight the role of inflammation and kidney function markers in identifying high-risk individuals, improving patient management, and mitigating complications. Monitoring these biomarkers remains crucial for managing long-term health impacts and future outbreaks