This study investigated corneal endothelial cell density (ECD) in pseudoexfoliation (PEX) syndrome patients and evaluated the clinical factors associated with ECD for 51 eyes of 41 phakic patients with pseudoexfoliation (PEX group) and 201 eyes of 117 patients with age-related cataracts (control group) as an age-matched control to the PEX group. Variable clinical factors, including ECD, central corneal thickness (CCT), anterior chamber depth (ACD), number of anti-glaucoma eye drops and severity of PEX, were examined using multivariate analyses. Severity of PEX was as follows: Mild in 28 eyes, Moderate in 16 eyes, and Severe in 7 eyes. The mean ECD was 2,548 ± 409 cells/mm2 in the PEX group and 2,757 ± 282 cells/mm2 in the control group, respectively, and ECD in the PEX group was significantly lower than that in the control group (P = 0.02). Multivariate analyses revealed that the severity of PEX [-176.8, 95% confidence interval (CI) (-244.5, -109.2), P < 0.01] was significantly associated with lower ECD. Accumulation of PEX materials contributed to early corneal endothelial decompensation.