Limited data exist to guide antimicrobial therapy commonly prescribed to patients undergoing extracorporeal membrane oxygenation (ECMO). This study aimed to describe the kinetics of the cefazolin, doripenem, daptomycin, and levofloxacin in heparin-coated and Xcoating ECMO circuits. Circuits were primed with bovine whole blood and maintained at a physiological pH and temperature for 24 h. Each antimicrobial agent was added to the whole blood before priming. Equivalent doses of these drugs were added to glass jars containing fresh bovine whole blood as a control. Serial blood samples were collected from the ECMO circuits and controls over 24 h, and drug concentrations were quantified using validated assays. The concentrations of cefazolin, doripenem, daptomycin, and levofloxacin did not decrease significantly over 24 h. Collectively, these antimicrobial agents can be administered without the need to consider sequestration when using either heparin-coated or Xcoating circuits.