Chlamydia trachomatis is the most prevalent sexually transmitted infection in the world and the leading cause of infertility in women. To date, infertility in Chlamydia-infected women has been solely attributed to pelvic inflammatory disease and scarring of the Fallopian tubes. However, fertility is also decreased in women without tubal damage, suggesting that additional reproductive pathologies exist. In this study, we investigated the hypothesis that Chlamydia can infect and damage the ovary. Balb/C mice (7 weeks-old) were sham infected or vaginally inoculated with 5 x 104 IFU Chlamydia muridarum (n=3-8/group/time point). At 6 days (during the acute phase of infection), Chlamydia was detected within ovarian macrophages and granulosa cells using qPCR and immunofluorescence. FACS analyses revealed that ovarian infection was accompanied by significant local recruitment of neutrophils, NK cells, macrophages and CD4+ T cells. Furthermore, intra-ovarian mRNA levels of pro-inflammatory cytokines, CXCL16, IL6 and IFNγ, were significantly elevated. Strikingly, primordial follicles were dramatically depleted in infected animals compared to controls (Sham: 3620 vs. Infected: 1865; p<0.05). At 35 days, active infection was cleared from the lower reproductive tract, but Chlamydia was still detectable in the ovary. Immune cells, such as macrophages and CD8+ T cells, and the expression of pro-inflammatory cytokines, such as TNFα and IL1α, were elevated in ovaries from infected animals compared to controls. This prolonged inflammatory response was associated with increased ovarian fibrosis in ovaries collected 100 days after infection, along with poorer oocyte in vitro maturation and in vitro fertilization success rates. Collectively, these data demonstrate that Chlamydia can penetrate the ovary and induce a sustained immune response, resulting in depletion of the ovarian follicular reserves and reduced oocyte quality. These findings suggest that damage to the ovary caused by Chlamydia is permanent and may underlie some cases of unexplained infertility and poor IVF outcome in women.