Aim:To evaluate the biochemical profile of complications in individuals presenting with acute febrile illness and to assess its role in diagnosing, prognosticating, and managing the disease. Material and Methods:This prospective observational study was conducted in the Department of Medicine with 200 patients aged above 14 years presenting with acute febrile illness and associated complications. Patients were evaluated through detailed histories, baseline investigations, and disease-specific diagnostic tests, including complete hemograms, liver and renal function tests, and ELISA-based diagnostic assays for infections like dengue, malaria, and hepatitis. Outcomes, including complications and mortality, were documented, and statistical analyses were performed using SPSS version 24.0. Results:Out of 2,211 cases of febrile illness, 200 (9%) required hospitalization. Diagnoses included dengue (30%), malaria (25%), enteric fever (20%), hepatitis E (15%), and mixed infections (10%). Common complications were hematological (10%), neurological (7.5%), hepatic (7.5%), and renal (4%) dysfunction. Mortality rates varied significantly by disease, with hepatitis E having the highest rate (10%, p=0.04). Laboratory findings showed elevated liver enzymes in 50%, thrombocytopenia in 35%, and renal impairment in 10%, highlighting the importance of biochemical markers in disease management. Conclusion:The biochemical profile in acute febrile illness is a valuable tool for identifying disease severity and complications. Key markers such as liver enzymes, renal function tests, and hematological parameters aid in early diagnosis, risk stratification, and therapeutic decision-making, especially in resource-limited settings. Standardized protocols and ongoing research are essential to optimize biochemical profiling for improved patient outcomes.