The administration of long-acting antimicrobial agents to treat susceptible bacterial infections in exotic animals is desirable, as it may reduce handling stress, increase therapeutic compliance, and decrease morbidity and mortality. Cefovecin sodium, a third-generation cephalosporin, is administered to treat susceptible bacterial infections in dogs and cats. Cefovecin has an extended dosing interval partially because of increased ability to bind with plasma protein. As such, investigations into the pharmacokinetics of this antibiotic have been conducted in zoo and exotic animal species, including terrestrial chelonians. The objective of this project was to determine the pharmacokinetic profile and protein binding of cefovecin in the red-eared slider (Trachemys scripta elegans). Eleven healthy red-eared sliders were administered 10 mg/kg of cefovecin subcutaneously in the forelimb. Blood samples were obtained at 2, 4, 8, 12, 24, and 48 hours postadministration. Plasma cefovecin concentrations were analyzed by reversed-phase high-performance liquid chromatography, and protein binding was determined using ultrafiltration. Noncompartmental pharmacokinetic analysis was performed on the resulting data. Cefovecin was rapidly absorbed, with a maximal measured plasma drug concentration of 32.3 (±23.8) μg/mL occurring at 2.4 (±1.2) hours and a terminal-phase half-life of 6.8 (±1.2) hours, which was much shorter than the half-life observed in dogs and cats (approximately 5 and 7 days, respectively). No substantial side effects were noted in subjects following antibiotic administration. Although well tolerated in red-eared sliders, the rapid decline in plasma cefovecin concentration, presumably due to the absence of plasma protein binding, negates its use as a long-acting antibiotic in this species.