Background: China's plasmapheresis donation policy differs from that of Western countries. The association between regular plasmapheresis donation and donor health in China is still unknown.

Objectives: To investigate the association of regular plasmapheresis donation with serum protein and electrolyte levels and provide scientific evidence for policy improvement.

Design: Multicentre cross-sectional study.

Setting and participants: A total of 767 regular and 726 new donors from the provinces of Sichuan, Hunan, Henan and Yunnan were recruited from September 2021 to October 2022.

Primary and secondary outcome measures: Our primary outcome focused on measuring the levels of serum protein and electrolyte levels, including total serum protein (TSP), IgG, albumin (Alb), haemoglobin (Hb), calcium, potassium (K⁺) and magnesium (Mg²⁺). The secondary outcome assessed their abnormal rates.

Results: Male and female donors in the high donation frequency group (>16 donations per year) exhibited lower IgG levels compared with new donors (p=0.008 for male donors and p=0.007 for female donors). Additionally, female donors with high donation frequency and a high total number of lifetime donations (>100 donations) had significantly lower Hb concentrations than new donors. However, no significant changes were observed in TSP, Alb, calcium, K⁺ and Mg²⁺ levels. There were also no statistically significant differences in the rates of abnormal protein and electrolyte values below the respective threshold levels between new and regular donors.

Conclusions: Plasmapheresis donation is not associated with an increased risk of abnormalities in the analysed parameters. However, the results provide preliminary evidence supporting the routine inclusion of IgG screening for donors, as plasmapheresis donation is associated with a decrease in IgG levels. Particular attention should be paid to the Hb levels of female donors, especially those who donate frequently. Testing of TSP at each donation may not be necessary.