Wolbachia endosymbionts are widespread intracellular, maternally inherited bacteria which manipulate the host to favour their spread through a population. Cytoplasmic incompatibility (CI) and viral suppression are two such manipulations driven by uncharacterised mechanisms. To gain insight into potential molecular mechanisms responsible for these effects, we performed the first in-depth proteomic characterisation of the host response to Wolbachia infection. We find that the presence of the Wolbachia wMelPop in Aedes aegypti mosquito cells alters levels of proteins involved in cell cycle control, DNA replication, autophagy, vesicular trafficking, iron homeostasis, amino acid degradation, purine metabolism, lipid metabolism and immunity. The majority of the cell cycle/DNA replication proteins were downregulated in the presence of Wolbachia, in particular, a member of the anoctamin family was strongly down regulated which may be related to the chromosomal segregation defects observed in CI crosses. We found clear evidence for perturbed lipid metabolism, Wolbachia infected cells expressed higher levels of Apolipoprotein D and the cholesterol efflux transporter ABCA1, while the LDL receptor and fatty acid synthase were downregulated. ABCA1 was also upregulated at the mRNA level in adult Wolbachia infected Aedes aegypti mosquitoes. Wolbachia therefore perturbs cholesterol homeostasis causing the host cell to respond to an apparent cholesterol excess which may contribute to viral inhibition.