Background: Despite similar frequencies of exposure, the low prevalence of certain sexually transmitted infections such as Chlamydia, HPV and HIV-1 in the oral cavity relative to the cervix is poorly understood. This could be explained in part by differences in host immune microenvironments between these two anatomic sites. Objective: We compared the concentration and correlation of 27 different immune markers in paired secretion specimens collected from the oral and cervical mucosa of healthy women. Methods: Paired oral and cervical secretion specimens were collected from thirty-nine women. The concentration of twenty-seven different immune markers was estimated using a Luminex multiplex assay. Marker concentration was normalized to total protein present in the specimen. Median immune marker concentrations were compared across anatomic sites. Unsupervised hierarchical clustering analysis was utilized to identify groups of markers that shared similar patterns of relative concentrations across anatomic sites. Results: The oral cavity had significantly higher concentrations of eotaxin, IFN-γ, IL-2, IL-4, IL-5, IL-7, IL-9, IL-13, IL-15, PDGF-BB, TNF-α, ( p<. 0.01 for each) while the cervix had higher concentrations of pro-inflammatory markers such as FGF-basic, IL-1ra, IL-1β, IL-6, IL-8, IP-10, G-CSF, GM-CSF, MCP-1, MIP-1β, VEGF ( p<. 0.01 for each). Hierarchical cluster analysis identified two groups of immune markers comprised of T-cell related immune markers with significantly higher concentrations in the oral cavity relative to the cervix, and a third cluster consisting of mostly inflammatory immune markers which were higher concentrations in the cervix. The oral cavity had a larger number of significant inter-marker correlations as compared to the cervix. Conclusions: The oral cavity and cervix have significantly different immune marker profiles, which may in part explain the significantly lower burden of sexually transmitted infections such as Chlamydia, HPV, and HIV-1 in the oral cavity vs. the cervix. © 2013 .