Introduction: Acute febrile illness is a major public health problem in north-eastern Uttar Pradesh and the adjoining regions of Bihar and Nepal. It leads to heavy morbidity and mortality. This study aims to find out what causes Multiple Organ Dysfunction Syndrome (MODS), how it shows up in a patient's body, and what other factors lead to it in our tertiary care hospital in the Eastern UP. Methodology: This observational study was done over one academic year (January 2018 to December 2018) with 200 patients attending the department of medicine at Nehru Hospital, B.R.D. Medical College, Gorakhpur. Results: In our study, mortality in MODS was significant in scrub typhus and without MODS was significant in dengue patients. It was found that serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and serum creatinine changes had significant p-value (.0001) for MODS patients. Conclusion: Out of known etiologies, 17.5% of scrub typhus, 10% of dengue, 2.5% of malaria, enteric fever dot, and sepsis can be prevented by educating people and taking preventive measures. Early hospitalisation and proper treatment can prevent these complications.