CA125 in peritoneal dialysis (PD) effluent dialysate has been used as a surrogate biomarker for the health of the peritoneum in PD patients. However CA125 is synthesised by epithelial cells and as such is not specific for the peritoneum, and most studies have only measured peritoneal CA125, without serum CA125 values. As such we wished to determine the factors which influenced PD effluent CA125 in a large contemporaneous cohort. We measured dialysate effluent CA125 in PD patients attending for routine assessment of peritoneal membrane function with a peritoneal equilibration test (PET), with corresponding serum CA125. Serum and dialysate CA125 were measured in 205 PD patients; 59.0 ± 16.8 years, median PD treatment 3 (2-20) months, 59 % male, 42.4 % diabetic, with 31.2 % treated by continuous ambulatory peritoneal dialysis, 22 % by automated overnight peritoneal dialysis cycler (APD) and 46.8 % by APD with a day time exchange. The median serum CA125 was 21 (13-38) U/ml, with an effluent 4 h PD PET effluent of 20 (11.5-36.5) U/ml. PET PD effluent dialysate was associated with PET dialysate total protein (β 12.9, p < 0.001), serum CA125 (β 0.109, p = 0.002), residual renal function (β 0.53, p = 0.018) and age (β 0.145, p = 0.042) and negatively with the number of PD cycles/day (β -2.19, p = 0.001). There was no association with prior peritonitis episodes. PD effluent CA125 concentrations were associated with peritoneal protein losses and increased by the usage of higher glucose dialysates to compensate for loss of residual renal function.