Quorum　sensing　inhibitors　(QSIs)　are　considered　as　potentially　promising　alternatives　to　antibiotics,　while　their　compound　effects　on　activated　sludge　nitrification　system　are　not　known.　This　study　aimed　to　investigate　interactions　among　abundant-rare　genera,　functional　genes,　and　antibiotic　resistance　genes　(ARGs)　under　QSI　(2(5　H)-furanone)　and　antibiotic　(ofloxacin)　compound　stress,　their　post-effect,　and　signaling　molecule　effect　in　activated　sludge　nitrification　system.　High　concentrations　compound　stress　inhibited　nitrification　and　increased　total　nitrogen　removal　to　76.84%.　Extracellular　polymeric　substances　(EPS)　content　tended　to　decrease　with　increasing　compound　stress　concentrations,　and　post-effect　promoted　EPS　secretion,　while　signaling　molecule　effect　promoted　protein　content　more　significantly.　Microbial　community　structure　of　conditionally　abundant　taxa　was　significantly　altered　under　compound　stress.　Conditionally　rare　or　abundant　taxa　was　the　core　taxa　and　showed　abundant　positive　correlations　with　rare　taxa.　High　concentrations　compound　stress　promoted　the　proliferation　of　specific　nitrogen　removal　functional　genera　such　as　Mesorhizobium,　Hydrogenophaga　and　Rhodococcus,　the　expression　of　denitrification　functional　genes　such　as　nosZ　and　napAB　and　occurrences　of　ARGs.　Strong　co-expressions　were　observed　among　specific　ARGs　subtypes　and　functional　genes,　especially　with　denitrification　functional　genes,　and　further　promoted　by　post-effect　and　signaling　molecule　effect,　which　could　enhance　microbial　resistance　to　stress.　Microbial　communities　and　ARGs　had　significant　effects　on　nitrogen　removal　performance,　and　together　explained　21.80%　of　change.　This　study　emphasized　contributions　of　component　interactions　in　maintaining　performance.　©　2024　Elsevier　Ltd