Background: Contemporary Chlamydia trachomatis (CT) serologic assays offer improved sensitivity compared to older assays. These newer assays have been used to measure the systemic antibody response to urogenital infections, but the systemic anti-CT antibody response to extragenital CT infections remains poorly understood. The aim of this study is to identify if extragenital CT infections generate serum antibodies to CT. Methods: This is a cross-sectional study using enrollment data from ExGen, a longitudinal cohort study of 140 men who have sex with men in Seattle, Washington, 2016-2018. At enrollment, participants provided a serum sample, a urine sample (if clinically-indicated) and self-collected rectal and pharyngeal swabs for nucleic acid amplification testing (NAAT). Total IgG antibodies were measured from serum using the mixed peptide enzyme-linked immunosorbent assay, which utilizes 24 CT-specific peptides as antigens; this assay has been validated among women with genital CT with a sensitivity of 86% using NAAT as a gold standard which is higher than most CT serological assays. We limited our analysis to participants who tested NAAT-positive for CT at enrollment. We used a comprehensive, regional electronic health record to assess whether participants had been previously diagnosed with CT at any time prior to enrollment. We calculated seroprevalence of total IgG anti-CT antibodies and Wilson 95% confidence intervals (CI), stratified by history of CT infection and anatomic site of infection. Results: There were 17 (12%) individuals who were NAAT-positive for CT at enrollment; of these, 8 (47%) had no documented prior CT infection. Among these 17 individuals with CT, the seroprevalence of total IgG antibodies to CT was 88.2% (95% CI: 62.2-97.9) and was 75.0% (95% CI: 35.6-95.5) for those without a history of CT (Table). Among participants with rectal CT, the seroprevalence was 85.7% (95% CI 56.1-97.5) overall and 66.7% (95% CI: 24.1-94.0) for those without a history of CT. For the few participants with pharyngeal and urethral CT infections, seroprevalence was 100%. Conclusion: Pharyngeal and rectal CT infections generate a systemic anti-CT antibody immune response. Future work could focus on the functional antibody response generated by extragenital CT. [ABSTRACT FROM AUTHOR]