Outer membrane vesicle (OMV) vaccines are effective at preventing invasive serogroup B meningococcal (MenB) disease caused by the homologous vaccine strain but demonstrate reduced efficacy against heterologous MenB strains. OMV specificity has been linked to antigenic diversity of immunodominant and abundant outer membrane proteins, like the porins PorA and PorB, and the membrane stabilizing protein RmpM. We previously reported that genetically detoxified (ΔLpxL1), detergent extracted OMVs (eOMVs) isolated from an unencapsulated (ΔSiaD) ΔPorAΔPorBΔRmpM strain (ΔABRSL) elicited bactericidal antibodies of greater titer and cross-reactivity relative to anti-wild-type (WT) detergent extracted, detergent detoxified OMV (dOMV) antibodies; similar results were observed when ΔABRSL eOMVs were compared to ΔABR dOMVs, isolated from a ΔPorAΔPorBΔRmpM strain that expresses LpxL1 and SiaD. All vaccines in the study were adsorbed using an aluminum hydroxide (Alhydrogel) adjuvant due to reactogenicity of the comparator WT and ΔABR dOMVs. However, Alhydrogel promotes Th2 skewing, which may not be beneficial for optimal immune responses. In this study, we tested the immunogenicity of ΔABRSL eOMVs when co-administered with adjuvants that stimulate varying immune responses. Adjuvanted ΔABRSL eOMV vaccines boosted total anti-MenB serum IgG antibody responses in male, but not female mice, relative to animals given ΔABRSL eOMVs alone. When tested in serum bactericidal activity (SBA) assays, co-administration of TLR4 adjuvants favored boosting of anti-MenB antibody titers in female mice alone; limited SBA was observed in male mice independent of immunization group, though mice given unadjuvanted ΔABRSL eOMVs showed the most consistent SBA. Ex vivo stimulation of splenocytes post-3rd immunization demonstrated an association between SBA and T helper cell skewing, as female and male mice favored Th1 and Th2 responses, respectively. The results suggest that ΔABRSL eOMVs may be (i) safely administered to mice in the absence of Alhydrogel and (ii) co-administered with alternate adjuvants to skew cellular and humoral immune responses in a sex-dependent manner.