Eastern indigo snakes (EIS; Drymarchon couperi) have unique physiological features that are not well understood. A useful tool to better understand the physiology of this species is reference intervals for plasma biochemical analytes; however, reported values for such analytes are often specific to the analyzer used. To determine whether a point-of-care analyzer would produce results comparable with those of a veterinary reference laboratory analyzer, this study aimed to compare plasma biochemical analyte values between these two types of analyzers, regardless of EIS health status. Plasma biochemical analyte values were obtained from 31 EIS and were compared between analyzers. The analytes were albumin (ALB), aspartate aminotransferase (AST), total calcium (Ca), creatinine kinase (CK), glucose (GLU), potassium (K), sodium (Na), phosphorus (P), total protein (TP), and uric acid (UA). A very high correlation between analyzers was found for AST (r = 0.923), K (r = 0.916), and UA (r = 0.965); a high correlation for Ca (r = 0.724), CK (r = 0.789), GLU (r = 0.889), and TP (r = 0.812); and a moderate correlation for P (r = 0.528), a low correlation for ALB (r = 0.471), and no correlation for Na (r = -0.138). A point-of-care analyzer offers many benefits such as portability, rapid results, small sample-size requirements, and the ability to use whole blood. The Vetscan VS2 point-of-care analyzer produces similar values for only some analytes, signifying the need for method-specific reference intervals for plasma biochemical analytes in EIS.