ObjectiveThe relationship among blood donation, cognition in blood donation and health condition of blood donors remains unclear. Based on our hypothesis, this study aimed to explore the mediating effect of cognition in blood donation on the relationship between blood donation and blood donors’ health status.MethodsA total of 837 participants who had prior experience in donating whole blood were recruited into a cross-sectional survey. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Questionnaire on Cognition in Non-remunerated Blood Donation were used to evaluate the health status and the level of cognition in blood donation, respectively. Blood donation referred to the cumulative times of blood donation. The mediating effect of cognition in blood donation was analyzed by applying a path model.ResultsThe results revealed that blood donation was positively related to the physical component summary (PCS) and mental component summary (MCS) of SF-36, and cognition in blood donation was shown to have a partial mediating effect on the relationship between blood donation and both PCS and MCS. The effect size of cognition in blood donation was 24.63% in PCS and 26.72% in MCS.ConclusionsBlood donation is positively correlated with SF-36 outcomes (PCS and MCS) of blood donors, and cognition in blood donation plays a partial mediating effect in the relationship between blood donation and PCS and MCS.