Objective To investigate the clinical and immunological characteristics of human immunodeficiency virus(HIV)-positive and HIV-negative monkeypox patients,and to clarify the impact of co-infection with HIV on the course of monkeypox. Methods A total of 54 monkeypox patients were enrolled from Shanghai Public Health Clinical Center from July 2023 to January 2024. Among them,31 patients were HIV-negative(people without HIV,referred to as the PWOH group) and 23 patients were HIV-positive(people with HIV,referred to as the PWH group). All the patients were classified into 0-3 d group,4-7 d group and >7 d group based on the time from onset to sample collection. The clinical data and 41 laboratory index determination results were collected,and plasma monkeypox virus nucleic acid and IgG antibodies,IgM antibodies and neutralizing antibodies were determined. Results Among the 41 laboratory indexes,there was statistical significance in white blood cell(WBC) count,the percentage of basophils(BASO%),the percentage of lymphocytes(LYMPH%),the absolute value of neutrophils(NEUT#) and albumin-to-globulin(A/G) ratio between PWH group and PWOH group(P<0.05). There was no statistical significance in clinical data,monkeypox virus nucleic acid positive rate and IgG antibodies,IgM antibodies and neutralizing antibodies between the 2 groups(P>0.05). In the >7 d group,there was statistical significance in WBC count,LYMPH%,BASO%,the percentage of neutrophils(NEUT%),NEUT#,A/G ratio,albumin(Alb) and cholinesterase(CHE) between HIV-positive and HIV-negative monkeypox patients(P<0.05),while in the 0-3 d group and 4-7 d group,there was no statistical significance in laboratory indexes between HIV-positive and HIV-negative monkeypox patients(P>0.05). In the 0-3 d group,4-7 d group and >7 d group,there was no statistical significance in monkeypox virus nucleic acid positive rate between HIV-positive and HIV-negative monkeypox patients(P>0.05). In the 0-3 d group,4-7 d group and >7 d group,there was no statistical significance in IgG antibodies,IgM antibodies and neutralizing antibodies between HIV-positive and HIV-negative monkeypox patients(P>0.05). Conclusions HIV-positive monkeypox patients who achieved immune reconstitution and have good control of HIV infection after antiretroviral therapy(ART) do not have their monkeypox condition worsened by co-infection with HIV,and it does not adversely affect the production of monkeypox virus antibodies.