Introduction: Elevated morbidity and mortality are linked to electrolyte imbalance (EI), which is prevalent in both hospitalized patients and the general population. According to reports, the frequency of hyponatremia in the emergency department (ED) ranges from 2.3% to 44%, whereas the prevalence of hypernatremia is between 1.4% and 4.4%, hypokalemia is between 10.2 and 39%, hyperkalemia is between 0.8 and 13%, and albumin-corrected hypercalcemia is between 0.7 and 7.5%. Measurement of Serum Electrolytes play a very vital role in diagnostics & treatment of patients. For many years, electrochemical sensors—ISEs in particular—have been widely employed for environmental and clinical investigation. Newer variants of ISEs are coming in market to minimize problems usually encountered in conventional ISEs. These machines have advantages over conventional ISEs. Authors, in this study compared to validate one new Cartridge based Ion Selective Electrode analyzer(Instrument A) with an existing conventional ISE analyzer(Instrument B). Material & methods: Thirty Five (35) numbers of Serum samples were selected, Analysis of Electrolytes done in both the instruments i.e. Instrument A &Instrument B. On Second Day Instrument A&B were compared by analysis of fluids with known Control values. Results: Linear Regression & Bland Altman plots were made from the results for Serum Sodium & Serum Potassium by the values obtained by Instrument A & B. Discussion: Linear Regressions shows positive correlation in both the instruments A & B. Both the Instruments showing Acceptable Values in respect to 2024 CLIA Acceptance Limits for Proficiency Testing by Westgard norms. Conclusion: It is concluded that Instrument A is non inferior to Instrument B.