An effective HIV vaccine has yet to be developed and defining immune correlates of protection against HIV infection is of paramount importance to inform future vaccine design. The complement system is a component of innate immunity that can directly lyse pathogens and shape adaptive immunity. To determine if complement lysis of SIV and/or SIV-infected cells represents a protective immune correlate against SIV infection, sera from previously vaccinated and challenged Rhesus macaques were analyzed for the induction of antibody-dependent complement-mediated lysis (ADCML). Importantly, the vaccine regimen, consisting of a replication-competent adenovirus type 5 host-range mutant SIV recombinant prime followed by a monomeric gp120 or oligomeric gp140 boost, resulted in overall delayed SIV acquisition only in females. Here, sera from all vaccinated animals induced ADCML of SIV and SIV-infected cells efficiently, regardless of sex. A modest correlation of SIV lysis with reduced infection rate in males but not females, together with reduced peak viremia in all animals boosted with gp140 suggested a potential for influencing protective efficacy. Gag-specific IgG, and gp120-specific IgG and IgM, correlated with SIV lysis in females while Env-specific IgM correlated with SIV43 infected cell lysis in males indicating sex differences in vaccine-induced antibody characteristics and function. In fact, gp120-/gp140-specific antibody functional correlates between ADCC, ADCP, and ADCML as well as gp120-specific IgG glycan profiles and corresponding ADCML correlations varied depending on the sex of the vaccinees. Overall, these data suggest that sex influences vaccine-induced antibody function which should be considered in design of globally-effective HIV vaccines in the future. [ABSTRACT FROM AUTHOR]