Helicobacter pylori (H. pylori) infection is prevalent worldwide and results in chronic gastritis, which may lead to peptic ulcer disease or gastric cancer. The goal of this study was to determine the role that H. pylori lipopolysaccharide (LPS) plays in stimulating host immune responses in the context of a vaccine. We compared H. pylori SS1 sonicate (LPS+) to a sonicate depleted of LPS (LPS-) in immunized BALB/c mice. Naïve splenocytes produced high levels of TNF-alpha and IL-10 after incubation with LPS+ sonicate, while cells incubated with LPS- sonicate did not. Mice immunized with LPS+ sonicate developed a prominent innate response characterized by increased TNF-alpha and IL-10, as well as a strong antigen specific Th1 response including, IFN-gamma, IL-2 and high IgG2a serum titers. Mice that received LPS- sonicate were strongly Th2 biased in their immune response, with significantly more IL-4 than IFN-gamma and serum IgG1 titers higher than IgG2a. Together these studies suggest that H. pylori LPS in a whole cell sonicate vaccine promotes a Th1 immune response that may aid in protection or clearance of H. pylori infection.