Introduction: Mechanical ventilation is used to assist or replace spontaneous breathing. It is implemented with special devices that can support ventilator function and improve oxygenation through the application of high–oxygen–content gas and positive pressure. Electrolytes and fluid disorders are ubiquitous in critically ill patients especially who are mechanically ventilated. Electrolytes disturbance have great impact on outcome during course and weaning from mechanical ventilation. This study is undertaken to evaluate the association between serum electrolytes changes and mechanical ventilation and their possible impact on prognosis and outcome. Aims & Objectives: To study the level of serum electrolytes in mechanically ventilated patients, To identify commonest electrolyte abnormality in mechanically ventilated patients, To correlate its effects with patient outcome in terms of mortality Materials and Methods: During the course of June 2018 to June 2019, total 100 subject requiring mechanical ventilation were undertaken examined into this prospective study. Estimation of serum electrolytes including Na+, K+, Ca++ and Cl– were done before ventilation and after the 24 hour interval of ventilation. Obtained data were plotted in excel sheet. APACHE II score was counted at the interval of 24 hours. Result: Out of 100 subjects, 55 were males with mean age of 46 ± 19 years and 45 were females with mean age of 42 ± 19 years. On comparison of data of serum electrolytes collected before ventilation and at 24 hours of mechanical ventilation with paired T test, it is noticed that there is statistically significant decrement in mean serum sodium, potassium and ionized calcium level at 24 hour interval of mechanical ventilation with difference of 3.15, 0.484 and 0.0485 respectively and P value of <0.0001, <0.0001 and 0.0075 respectively. we observed an incidence of electrolyte imbalance at the interval of 24 hours of mechanical ventilation in the form of Hypocalcemia (75%), Hyponatremia (45%), Hypokalemia (41%), and Hypochloremia (41%). Conclusion: Patients requiring on mechanical ventilation are at a higher risk of decrease in plasma Sodium, Potassium and Calcium(ionized) level. Intensive treatment during the period of stay on mechanical ventilation added to the disease process itself can cause further deterioration in the level of serum electrolytes. Imbalance of serum electrolytes and delay in time for its correction increase the period of mechanical ventilation, prolongs the stay in critical setup and associated with increment of co–morbidity and mortality.