Wolbachia pipientis is a ubiquitous intracellular bacterium that is known for its manipulation of reproduction in arthropod hosts. Wolbachia has also been shown to colonize virtually all somatic tissues, including the brain, but little is known about the interaction between host and bacterium in these locations. To this end, we studied the effects of Wolbachia infection on the brain of Drosophila melanogaster. Using comparative proteomics, we uncovered the post-translational modification of many proteins within the Drosophila head and body upon infection, with glutamic acid decarboxylase being modified within the head only. Given this enzyme’s role in neurotransmitter synthesis, we next tested how Wolbachia infection impacts various behaviors and GABA production within Drosophila. We discovered an improved response to yeast odors in Wolbachia-infected, mated females compared to their uninfected counterparts. Gross measurements of GABA in whole brains showed no detectable change in GABA abundance upon infection. Treatments with GABA agonist indicated that the behavioral change was not GABA-dependent, leaving the mechanism behind Wolbachia-mediated changes in behavior obscure. Given the multiple protein changes in the Drosophila head upon infection, we propose a model in which Wolbachia drives the modification of glutamic acid decarboxylase, and several metabolic proteins, to increase survival in the specialized niche of the brain. These results give rise to new questions about the Wolbachia-Drosophila relationship and future work will focus on the mechanism through which Wolbachia confers these protein changes.