Hyperviscosity syndrome (HVS) is a condition in human medicine where the patient’s blood becomes excessively viscous leading to neurological deficits, visual disturbances, and mucosal bleeding. While not commonly reported in veterinary medicine, the condition is typically associated with paraneoplastic syndrome, 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 a plasma viscosity reference interval for EIS. Plasma from 54 adult EIS in human care was evaluated with a portable viscometer (microVISCTM, RheoSense, Inc.). 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. Further studies are needed, evaluating tissues of EIS with plasma viscosity above this reference interval for histologic signs consistent with HVS.