The　causal　effects　of　mental　health　problems　on　the　risk　of　infectious　diseases　remain　vague.　Investigating　them　via　observational　study　is　challenging　as　it　presents　possible　confounding　factors.　Therefore,　the　objective　of　this　study　was　to　utilize　Mendelian　randomization　(MR)　techniques　to　evaluate　the　causal　relationship　between　mental　health　problems　and　the　risk　of　infectious　diseases.　Multivariable　MR　analyses　were　performed　using　genome-wide　association　data　for　sleep　disorders　(N = 216,700),　depression　(N = 500,199),　anxiety　(N = 290,361),　nervous　feelings　(N = 450,700),　unspecified　mental　disorder　(N = 218,792),　pneumonia　(N = 486,484),　skin　and　subcutaneous　tissue　infection　(SSTI;　N = 218,792),　intestinal　infectious　diseases　(IIDs;　N = 218,792),　urinary　tract　infection　(N = 463,010),　and　central　nervous　system　(CNS)　infections　(N = 218,792)　among　individuals　of　European　ancestry.　Independent　genetic　variants　significantly　(P ＜ 10-8)　associated　with　each　exposure　were　considered　instruments.　The　primary　analysis　used　an　inverse　variance-weighted　method,　followed　by　a　series　of　sensitivity　analyses.　Genetically　predicted　sleep　disorders　were　associated　with　an　increased　risk　of　SSTI　(odds　ratio　[OR],　1.29　[95%　confidence　interval　(CI),　1.05-1.59];　P = .017).　Genetically　predicted　depression　was　linked　with　an　increased　risk　of　CNS　infections　(OR,　1.59　[95%　CI,　1.00-2.53];　P = .049)　and　SSTI　(1.24　[95%　CI,　1.03-1.49];　P = .024).　Genetically　predicted　anxiety　was　associated　with　IIDs　(OR,　1.19　[95%　CI,　1.03-1.37];　P = .017)　and　SSTI　(OR,　1.21　[95%　CI,　1.02-1.43];　P = .029).　There　was　no　significant　causal　evidence　for　genetic　prediction　of　nervous　feelings　and　unspecified　mental　disorders　in　IIDs,　CNS　infections,　SSTI,　pneumonia,　or　urinary　tract　infection.　Sensitivity　analyses　showed　that　the　above　causal　association　estimates　were　robust.　In　this　MR　study,　we　demonstrated　a　causal　relationship　between　sleep　disorders,　depression,　anxiety,　and　the　risk　of　infectious　diseases.　However,　no　evidence　was　found　to　support　causality　between　nervous　feelings,　unspecified　mental　disorders,　and　the　risk　of　infectious　diseases.　©　2024　Lippincott　Williams　and　Wilkins.　All　rights　reserved.