Introduction and Hypothesis <p>This study was conducted to investigate the associations between baseline absolute monocyte count (AMC), absolute lymphocyte count (ALC), the platelet-to-lymphocyte ratio (PLR), and the risk of mesh exposure following transvaginal mesh (TVM) surgery for pelvic organ prolapse (POP).</p> Methods <p>This prospective cohort study included 206 symptomatic POP patients who underwent TVM treatment with titanium-coated polypropylene mesh (Tiloop) from June 2015 to December 2021 at Peking Union Medical College Hospital. Patients were classified into mesh exposure (<i>n</i> = 23) and non-exposure (<i>n</i> = 183) groups. Baseline hematological indicators, including AMC, ALC, PLR, the neutrophil-to-lymphocyte ratio, the lymphocyte-to-monocyte ratio, and the prognostic nutritional index, were recorded. Restricted cubic spline (RCS) analysis and Cox proportional hazards models were used to assess the associations between these indicators and mesh-exposure risk.</p> Results <p>Mesh exposure occurred in 11.2% of the patients. Significant differences in AMC, ALC, and PLR were detected between the exposure and non-exposure groups. RCS analysis revealed inverse linear associations between AMC and ALC and mesh exposure risk and a positive linear association for the PLR. Lower AMC (adjusted hazard ratio [aHR] = 0.424; 95% CI 0.228–0.786) and ALC (aHR = 0.422; 95% CI 0.255–0.698) were associated with increased mesh exposure risk, whereas higher PLR (aHR = 2.170; 95% CI 1.486–3.169) was associated with increased risk.</p> Conclusion <p>Low AMC and ALC and elevated PLR were independently associated with an increased risk of mesh exposure after TVM surgery.</p>