The　prevalence　of　antibiotics　poses　a　serious　challenge　to　biological　nitrogen　removal　in　wastewater.　In　this　study,　the　effects　of　sulfamethoxazole　and/or　trimethoprim　(15　mg/L　similar　to　30　mg/L)　on　treatment　performance,　nitrogen　transformation　and　antibiotic　resistance　genes　(ARGs)　were　investigated　in　aerobic　activated　sludge　systems　to　elucidate　the　metabolic　mechanism　under　high　antibiotic　stress.　15　mg/L　single　antibiotic　stress　improved　total　nitrogen　removal　performance　due　to　the　persistence　of　nitrifiers　and　enrichment　of　denitrifiers,　with　an　optimum　removal　efficiency　of　96.5　%.　Up-regulation　of　all　denitrifying　genes,　coupled　with　enhanced　electron　transfer　of　Complex　II　and　III,　contributed　to　the　emergence　of　aerobic　denitrification.　The　increased　expression　of　antioxidant　genes　also　alleviated　intracellular　pressure.　Whereas　combined　antibiotic　stress　induced　the　significant　down-regulation　of　denitrifying　bacteria　and　genes　(nirKS　and　nosZ),　and　suppressed　the　electron　supply　for　denitrification　by　restraining　genes　related　to　Complex　I　and　energy　supply　by　tricarboxylic　acid　cycle,　driving　the　collapse　of　activated　sludge　system,　with　ammonia　and　total　nitrogen　removal　efficiencies　dropping　to　below　40　%　and　20　%,　respectively.　The　dominant　genera　in　system　changed　from　TM7a　to　Thiothrix　and　Sphaerotilus　with　increasing　antibiotic　concentration　and　type.　Moreover,　antibiotic　stress　promoted　a　slight　enrichment　of　ARGs,　especially　those　encoding　efflux　mechanisms.　Cooperative　relationships　(＞　93　%)　dominated　among　ARGs,　and　Klebsiella　was　identified　as　the　crucial　host.　ARGs　regulating　antibiotic　efflux　were　more　likely　to　be　co-expressed　with　functional　genes.　These　results　may　provide　a　theoretical　basis　for　establishing　promising　strategies　to　mitigate　antibiotic-caused　process　deterioration.