Multiple　nanoparticles　presented　in　wastewater　treatment　plants　can　produce　comprehensive　ecotoxicity.　In　this　study,　copper　oxide　nanoparticles　(nCuO)　and　zinc　oxide　nanoparticles　(nZnO)　were　investigated　for　their　cotoxicity　to　aerobic　granular　sludge　(AGS)　systems.　The　combined　stress　of　nCuO　and　nZnO　performed　significant　antagonistic　effects　on　nitrogen　removal　both　under　acute　and　chronic　stress.　Under　chronic　stress,　nCuO　and　nZnO　co-existence　performed　significant　antagonistic　effects　on　cell　membrane,　adenosine　triphosphate　(ATP)　activity　and　microbial　community　structure.　PICRUSt　analysis　indicated　that　nCuO　(15　mg/L)　co-existence　alleviated　nZnO　(10　mg/L)　inhibition　on　energy　production　and　membrane　transport　metabolic　pathways.　In　addition,　nCuO　addition　to　single　nZnO　weakened　the　toxicity　of　nZnO　to　nitrogen　metabolism,　glucose　metabolism,　and　electron　transfer　genes,　contributing　to　an　alleviation　in　nitrogen　removal　inhibition.　As　compared　with　individual　stress,　combined　stress　decreased　Cu(II)　release　from　nCuO,　but　increased　Zn(II)　release　from　nZnO.　The　combination　of　nCuO　and　nZnO　increased　zinc　resistance　gene　amplification　and　czcC　gene　proportion,　and　promoted　Zn(II)　efferent　from　cells,　also　with　AGS　resistance.