The　combined　pollution　of　antibiotics　and　heavy　metals　has　become　a　research　hotspot　in　the　field　of　environmental　research.　However,　studies　on　the　ecological　effects　of　the　combined　pollution　on　activated　sludge　systems　have　mainly　focused　on　the　bacterial　community,　ignoring　the　archaeal　community,　which　plays　several　important　roles.　In　this　study,　azithromycin　(AZM)　and　copper　(Cu)　were　selected　to　investigate　the　short-term　and　post-effect　of　different　concentrations　of　AZM　(0.05-40　mg•L-1)　on　an　archaeal　community,　antibiotic　resistance　genes　(ARGs),　and　their　interactions　at　low　temperatures　when　copper　was　maintained　at　1　mg•L-1.　The　results　showed　that　the　diversity　of　archaea　increased　with　the　increase　in　AZM　concentration;　however,　the　richness　decreased,　and　both　recovered　to　a　certain　extent　during　the　post-effect　period.　It　was　found　that　different　concentrations　of　AZM　led　to　variations　in　microbial　community　structure　based　on　the　full-scale　classification　method.　The　archaeal　community　structure　was　divided　into　three　groups,　and　the　post-effect　influence　was　not　obvious.　The　effects　of　combined　pollution　on　the　structure　of　the　abundant　taxa　were　greater　than　that　of　the　rare　taxa.　Moreover,　the　variation　in　the　conditionally　rare　taxa　(CRT)　was　consistent　with　that　of　the　whole　archaeal　community.　There　were　specific　genera　with　different　resistance　and　recovery　characteristics　in　different　taxa,　which　had　different　responses　to　the　combined　pollution　of　AZM　and　copper.　The　resistance　of　abundant　taxa　to　combined　pollution　was　significantly　stronger　than　that　of　the　rare　taxa,　of　which　Methanosaeta,　Methanobacterium,　and　Methanosarcina　were　the　dominant　resistant　archaeal　genera.　A　total　of　29　ARGs　were　obtained　using　prediction　analysis,　and　AZM　caused　the　proliferation　of　ARGs,　especially　at　high　concentrations;　however,　the　effects　on　each　subtype　of　ARGs　were　different.　The　co-occurrence　patterns　were　mainly　observed　among　the　archaeal　community　and　ARGs　during　the　stress-effect　and　post-effect　periods.　Among　them,　CAT　was　the　core　taxa　in　the　microbial　interaction　network.　However,　rare　taxa　(RT)　represented　an　important　ecological　niche　during　the　stress-effect　period.　Meanwhile,　both　co-occurrence　and　co-exclusion　patterns　existed　among　ARGs.　A　variety　of　archaeal　genera　were　positively　correlated　with　ARGs,　and　they　were　the　potential　hosts　of　ARGs.　In　particular,　Methanobrevibacter　and　Methanolobus　may　carry　a　variety　of　ARGs.　Overall,　this　study　could　provide　new　insight　and　theoretical　basis　for　the　risk　assessment　of　the　combined　pollution　of　antibiotics　and　heavy　metals　in　wastewater　treatment　systems　and　the　removal　of　ARGs.　©　2021,　Science　Press.　All　right　reserved.