The status of the erythrocyte antioxidant defense system and its relationship to posttransfusion red cell survival were determined in erythrocytes stored for 35 or 42 days in CPD‐A1 anticoagulant with a saline‐adenine‐glucose additive. As storage progressed, there was a significant increase in incubated Heinz body formation (P < .001) and a significant decrease in reduced glutathione (GSH) stability (P < .001). Stimulated pentose phosphate shunt activity also declined during storage (P < .06), while unstimulated shunt activity remained unchanged. The increase in Heinz body formation was associated with decreased GSH stability (r = –.77, P < .001), which in turn was associated with the decline in stimulated pentose shunt activity (r = .67, P < .001). The changes in Heinz body formation (r = ‐.85), GSH stability (r = .83). and stimulated pentose shunt activity (r = .54) were all significantly (P < .001) related to the decline in adenosine triphosphate (ATP) content of the erythrocyte. Red cell survival 24 hours after transfusion was significantly related to the GSH stability (r = .80, P < .001) and to the ATP concentration (r = .76, P < .005) on the day of transfusion. Thus, dysfunction of the erythrocyte antioxidant defense system occurs during blood storage and appears to be related, in part, to ATP depletion. The ability to maintain a normal reduced glutathione concentration during oxidant stress appears to be an important determinant of red cell survival in the peritransfusion period.