The continuing discovery and development of adjuvants for vaccine formulation is important to safely increase potency and/or reduce antigen dose of existing vaccines, and tailor the adaptive immune response to newly-developed vaccines. Adjuplex™ is a novel adjuvant platform based on purified lecithin and carbomer homopolymer. Here we analyzed the adjuvant activity of Adjuplex™ in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A. Titration of Adjuplex™ revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific HA, but inducing no significant weight loss. At this dose, Adjuplex™ completely protected mice from an otherwise lethal influenza challenge, and was at least as effective as adjuvants MPL and alum in preventing disease. Adjuplex™ elicited a balanced Th1/Th2-type immune response with accompanying cytokines, and triggered antigen-specific CD8(+) T cell proliferation. Use of the peritoneal inflammation model revealed that Adjuplex™ recruited dendritic cells (DCs), monocytes and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex™ neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NFκB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex™ as a potent and well-tolerated adjuvant with application for subunit vaccines.