In　single-atom　catalysts　(SACs),　the　single　atoms　are　often　exposed　as　protrusions　above　the　substrate.　The　solvent　molecules　in　the　electrocatalytic　environment　can　interact　or　even　bind　to　these　coordination-unsaturated　single　atoms　and　thus　influence　the　reaction　process,　but　this　has　not　been　studied　in　depth.　In　this　work,　we　systematically　investigate　the　thermodynamics　of　CO2　reduction　reaction　(CO2RR)　to　CO　over　MoS2-supported　single　metal　atom　catalysts　(TM@MoS2,　TM　=　transition　metal)　under　vacuum　and　explicit　solvent　environments　using　density　functional　theory.　In　addition,　the　ab　initio　molecular　dynamics　results　show　that　explicit　H2O　molecules　can　coordinate　to　the　TM　site　and　undergo　competitive　adsorption　with　the　CO2RR　intermediates,　which　significantly　affects　the　energy　and　conformation　of　the　CO2RR　pathway.　Electronic　structure　analysis　reveals　that　the　occupying　H2O　molecules　change　the　electronic　state　of　single　atom　and　further　influence　the　adsorption　strength　of　different　CO2RR　intermediates.　Our　work　shows　that　water　molecules　can　not　only　act　as　ligands　to　influence　the　electronic　state　of　TM,　but　also　affect　the　energy　and　conformation　of　CO2RR　intermediates,　which　highlights　the　important　role　of　occupying　H2O　molecules　at　the　single-atom　sites　in　CO2RR　and　provides　useful　insights　for　the　design　of　SACs　for　efficient　CO2RR.[Figure　not　available:　see　fulltext.].　©　2023,　Tsinghua　University　Press.