Nosocomial infections caused by multidrug-resistant (MDR) bacteria is treated with Linezolid (LIN) either alone or with other medications such as; Meropenem (MERO) or Theophylline (THEO). LIN has variable pharmacokinetics which makes it an ideal candidate for therapeutic drug monitoring (TDM). Ion selective electrode (ISE) is a promising tool that can be used in hospitals by medical practitioners to adjust the dose of LIN which will eventually improve the therapeutic outcomes. Four potentiometric PVC sensors were fabricated for the determination of LIN in plasma in the presence of co-administered medications (MERO and THEO). Sensor I; cationic exchanger phosphotungstate sensor covering a concentration range of 1.0 x 10(-7)-1.0 x 10(-4) M. while Sensor II; 2-hydroxypropyl-beta-cyclodextrin (HP-beta CD) sensor covered a concentration range of 1.0 x 10(-9)-1.0 x 10(-3) M. The last two sensors were fabricated using metal nanoparticles (NPs). Sensor III; Copper NP-incorporated HP-beta CD sensor was used over a concentration range 1.0 x 10(-9)-1.0 x 10(-3) M, while Sensor IV; Cobalt NP-incorporated HP-beta CD sensor attained the highest sensitivity of all the prepared sensors with the quantification range of 1.0 x 10(-10)-1.0 x 10(-4) M. Britton-Robinson buffer at pH 3.5 +/- 0.5 was chosen for optimization of experimental conditions of the four sensors. The proposed sensors performance was validated according to IUPAC\FDA guidelines and was applied successfully for the determination of LIN in its pharmaceutical formulation and for TDM in incurred plasma samples. No interference was noted in the presence of (MERO) and (THEO) that are commonly co-administered with LIN as a part of the treatment protocol for healthcare-associated pneumonia (HCAP). (C) 2019 The Electrochemical Society.