Background: Use of different analyzers to measure electrolytes in the same horse can lead to different interpretation of acid-base balance when using the simplified strong ion difference (sSID) approach. Objective: Investigate the level of agreement between 2 analyzers in determining electrolytes concentrations, sSID variables, and acid-base disorders in sick horses. Animals: One hundred twenty-four hospitalized horses. Methods: Retrospective study using paired samples. Electrolytes were measured using a Beckman Coulter AU480 Chemistry analyzer (PBMA) and a Nova Biomedical Stat Profile (WBGA), respectively. Calculated sSID variables included strong ion difference, SID 4 ; unmeasured strong ions, USI; and total nonvolatile buffer ion concentration in plasma (A tot). Agreement between analyzers was explored using Passing-Bablok regression and Bland-Altman analysis. Kappa (κ) test evaluated the level of agreement between analyzers in detecting acid-base disorders. Results: Methodologic differences were identified in measured Na + and Cl − and calculated values of SID 4 and USI. Mean bias (95% limits of agreement) for Na + , Cl − , SID 4 , and USI were: −1.2 mmol/L (−9.2 to 6.8), 4.4 mmol/L (−4.4 to 13), −5.4 mmol/L (−13 to 2), and −6.2 mmol/L (−14 to 1.7), respectively. The intraclass correlation coefficient for SID 4 and USI was .55 (95%CI: −0.2 to 0.8) and .2 (95%CI: −0.15 to 0.48), respectively. There was a poor agreement between analyzers for detection of SID 4 (κ = 0.20, 95%CI, 0.1 to 0.31) or USI abnormalities (κ = −0.04, 95% CI, −0.11 to 0.02). Abbreviations: A − , total net negative charge of plasma proteins; AG, anion gap; Atot, total plasma concentration of nonvolatile weak acids; HCO3 − , bicarbonate; ICC, intraclass correlation coefficient; L-lac − , L-lactate; P v CO 2 , venous partial carbon dioxide pressure; SID, strong ion difference; SIDm, measured strong ion difference; SIG, strong ion gap; sSID, simplified strong ion difference approach; TP, total protein; TS, total solids; USI, unmeasured strong ions.