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Abstract Hyperviscosity syndrome (HVS) is a condition in human medicine where the patient’s blood becomes excessively thick or viscous, leading to neurological deficits, visual disturbances, and mucosal bleeding. While not commonly reported in veterinary medicine, the condition is typically associated with paraneoplastic syndromes, erythrocytosis, and hypergammaglobulinemia. HVS was first described in reptiles in 2008, and additional cases have subsequently been reported in various squamate species, including the eastern indigo snake (EIS, Drymarchon couperi), a threatened species native to the southeastern region of the US. The most common presentation of HVS in snakes is sudden death, necessitating an ante-mortem screening test. The aim of this study was to determine if plasma viscosity could be readily measured in EIS and whether the results could be associated with clinical disease. Plasma from 54 adult EIS in human care was evaluated with a portable viscometer ( micro VISC TM , RheoSense, Inc., San Ramon, CA, USA). The viscosity readings were also compared to select plasma analytes to check for correlations. There was not a significant difference in plasma viscosity between the sexes (P = 0.877), and these values were combined, creating a sample size large enough to compute a nonparametric reference interval of 1.915 – 4.778 cP with 90% confidence intervals of 1.872 – 2.096 cP and 4.562 – 4.780 cP, respectively. There was also a very high positive correlation of plasma viscosity with plasma total solids (⍴ = 0.90). Additionally, two case studies are briefly outlined where the plasma viscosity results support clinical disease and suggest acute and chronic presentations of HVS in EIS. Measurement of plasma viscosity may serve as a valuable ante-mortem diagnostic tool for early detection of HVS and related disorders in reptiles and further studies are needed to evaluate HVS case management options.