A parenteral medical combination containing vaborbactam and meropenem is used mainly to treat complicated urinary tract infections. A novel ultra-performance liquid chromatography tandem mass spectrometric method was developed for the sensitive determination of both compounds in human plasma. Sample preparation was performed by precipitation technique. The chromatographic separation was accomplished using the Acquity C18-BEH column, 0.01 M ammonium formate: acetonitrile (47 : 53, v/v) as a mobile phase with a flow rate of 0.2 ml min ⁻¹ . Analytes were monitored by applying multiple reaction monitoring. The bioanalytical validation criteria were conducted following the Food and Drug Administration recommendations. The method was linear within range 0.5 to 50 µg ml ⁻¹ , for both drugs. The intra-day and inter-day precision, as coefficient variation (% CV) and the accuracy, as % bias did not exceed 15% for both drugs. The percentage recovery of targeted analytes was not less than 77%, calculated at three quality control levels. The proposed method showed a suitable lower level of quantification value of 0.50 µg ml ⁻¹ for both analytes, which is far lower than the expected C _max , which permits the use of this method for pharmacokinetic studies. The proposed method proved to be useful for the evaluation of this combination in both human plasma and pharmaceutical formulation.