Abstract CuO nanosheets were synthesized by an easy and green sonochemical method. It was found that, CuO nanosheets could significantly catalyse the chemiluminescence (CL) reaction of luminol–KMnO4 in an alkaline condition. Based on this finding, a new CL system (luminol–KMnO4–CuO nanosheets) combined with flow injection analysis has been developed for the determination of meropenem for the first time. Moreover, the CL intensity was enhanced when meropenem was presented in the reaction system. Under the optimum conditions, the enhanced CL intensity was proportional to the concentration of meropenem in the ranges of 0.005–6.00mg L−1, with a detection limit (3σ) of 0.0036mg L−1. The precision of the method was calculated by analyzing samples containing 1.0mg L−1 meropenem (n=11) and the relative standard deviation (RSD) was 1.7%. Also, a total analysis time per sample was 30seconds which confirmed the rapidity of the proposed assay. The practicality of the proposed CL system was evaluated by determining meropenem in spiked environmental water samples and human serum. A discussion on the possible CL reaction mechanism was also presented.