Objectives:We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia.Design:We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children’s Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions.Setting:PICU of a quaternary, free-standing children’s hospital.Patients:Children admitted to the hospital who received vecuronium and/or esmolol infusion.Measurements and Main Results:Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel–blood gas) sodium within 12 hours of the vecuronium administration (p < 0.0018). Esmolol showed a similar trend (p = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions.Conclusions:Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.