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Cefoperazone is used in children with sus-pected or documented Gram-negative serious infections. Currently, its use is off-label partly because of lack of phar-macokinetic studies. Our aim was to evaluate the pop-ulation pharmacokinetics of Cefoperazone in children between 2–12 years of age and define the appropriate dose in order to optimise cefoperazone treatment in this vulnerable population.Blood samples were collected from children treated with Cefoperazone and concentrations were quantified by HPLC-MS. Population pharmacokinetic analysis was performed using NONMEM software.The data from 83 children (age range: 2.2–10.8 years) were available for population pharmacokinet-ic analysis. A two-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that current weight had a significant impact on cefoperazone pharmacokinetics.The population pharmacokinetics of Cefop-erazone was evaluated in children between 2–12 years old and an evidence-based optimal dosing regimen was established based on simulation.