Background: Dialysis may deplete the body of valuable solutes. We previously found that the diet-derived antioxidant ergothioneine was markedly depleted in hemodialysis (HD) patients. Standard peritoneal dialysis (PD) prescriptions provide lower clearances of small molecules than standard HD prescriptions. We therefore tested whether ergothioneine would be depleted in PD patients but to a lesser degree than in HD patients. Methods: Blood levels of ergothioneine were compared in 16 PD patients, 16 HD patients, and 15 controls with normal kidney function. Levels were measured using liquid chromatography mass spectrometry in plasma and also in erythrocytes in which ergothioneine is normally highly concentrated. Ergothioneine clearances by PD and HD were also compared. Results: Erythrocyte ergothioneine levels were much lower in both PD and HD patients than controls. The erythrocyte ergothioneine levels, however, were less depleted in PD patients than in HD patients. The erythrocyte levels in PD patients averaged 34% those of controls while levels in HD patients averaged only 10% those of controls. Plasma ergothioneine levels in dialysis patients were also lower than controls. The time-averaged clearance of ergothioneine was lower with PD than with HD, so that a standard PD regimen would remove less ergothioneine daily than a standard HD regimen at a given plasma level. Conclusions: The antioxidant ergothioneine is depleted in PD patients but to a lesser extent than in HD patients. Benefits of ergothioneine repletion in dialysis patients remains to be assessed.