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Background: The biological mechanisms underlying “chemo brain” or neurobehavioral symptoms in cancer patients are largely unknown, however, an emergent literature links indicators of immune deregulation to these symptoms. We hypothesized higher concentrations of pro-inflammatory cytokine interleukin 6 in breast cancer (BC) patients at both pre and post-treatment assessment relative to healthy controls, and that IL6 levels would be associated with changes in neurobehavioral functioning. Methods: Post-menopausal BC patients were assessed prior to any local or systemic treatment and one month after completion of primary treatment. Age-matched Healthy controls (HC) were assessed at similar time intervals. Neurocognitive, behavioral, and IL6 data for 120 BC and 56 HC were examined. Results: Statistically significant differences in IL6 levels between BC and HC were not evident at baseline but were at follow up assessment, with increased levels in the BC group. Factorial ANCOVA which evaluated pre-post treatment change in the BC and HC groups found that BC patients with higher IL6 levels at baseline had significant declines in selected cognitive functioning relative to the comparison groups, including memory retention (F (1,155)=7.07; p =.009) and processing speed (p =.055). Similar interaction effects were not found on measures of fatigue, mood, or pain. Conclusion: Breast cancer patients with higher IL6 levels prior to treatment appear to be at risk for worse functioning in selected behavioral outcomes following treatment. [ABSTRACT FROM AUTHOR]