Associations between benign gynecologic pathologies and circulating inflammatory markers are unknown. Our goal was to evaluate self-reported history of benign gynecologic pathology and subsequent alterations in systemic inflammation. Using nested case-control studies from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, study-specific associations between self-reported history of benign ovarian cysts, uterine fibroids, and endometriosis with inflammatory marker concentrations were evaluated using logistic regression and combined using meta-analysis. Inflammatory markers associated with individual benign pathologies were mutually adjusted for one another to evaluate independent associations. Compared to women without a self-reported history of the pathology evaluated, benign ovarian cysts were associated with increased PAI-1 (OR 95% CI 6.24 2.53–15.39, P <.001) and TGF-β1 (3.79 1.62–8.86, P =.002) and decreased BCA-1 (0.38 0.19–0.73, P =.004). Uterine fibroids were associated with decreased CXCL11 (0.37 0.22–0.63, P <.001) and VEGFR3 (0.40 0.24–0.65, P <.001). Endometriosis was associated with increased SIL-4R (4.75 1.84–12.26, P =.001). Self-reported history of benign gynecologic pathologies were associated with alterations in inflammatory markers that have been previously linked to cancer risk. Understanding interactions between benign gynecologic pathologies and the systemic immune system may help inform disease risk later in life.