Chlamydia trachomatis is the most commonly diagnosed sexually transmitted infection (STI) in Australia (1) and can cause severe and irreversible damage to the fallopian tubes, leading to ectopic pregnancies or complete infertility. Previous Chlamydia infections are also associated with elevated miscarriage rates, poor IVF outcomes and increased time to natural conception, suggesting that fertility may be compromised by mechanisms that extend beyond fallopian tube scarring. In this study, we used a well-characterised mouse model to investigate that hypothesis that Chlamydia infection, and the inflammatory response it induces, damages the ovary. Primordial and growing follicle numbers were found to be significantly reduced 35 days after a single infection compared to uninfected controls (p<0.05, n=4 mice/group). A second infection of Chlamydia caused a further decrease in the numbers of all follicle types (p<0.05, n=4-5 mice/group) and increased the proportion of follicles with apoptotic granulosa cells (p< 0.05, n=4-5 mice/group). Two infections was also associated with changes in the overall ovarian morphology and increased fibrosis in the ovary (p<0.05, n=5 mice/group). Notably, using immunohistochemistry, chlamydial bodies were detected in the ovarian stroma 35 days after a single or double infection, indicating persistence. Collectively, these observations provide evidence that Chlamydia penetrates the ovary and disrupts the ovarian reserve, ovarian function and the structural integrity of the ovary itself, suggesting that ovarian infection may underlie some cases of unexplained infertility and poor IVF outcome. The results obtained from this study will aid the development of improved therapeutic strategies, including novel vaccines, to reduce the damaging effects of Chlamydia infection.