Preoperative autologous blood donation (PABD) has been shown to decrease natural killer (NK) cell function in cancer patients, raising concerns about an increased cancer recurrence risk owing to PABD. It is unclear whether PABD leads to other immunomodulatory effects that might affect more short-term risks like postoperative infectious complications in surgical patients. Lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells, NK cells) were determined in 86 consecutive patients donating 2 units of autologous whole blood prior to elective hip replacement surgery. In addition, cytokine secretion patterns of monocytes [tumour necrosis factor (TNF)] and lymphocytes [interferon-γ, interleukin (IL)-2, IL-4, IL-10] upon stimulation were determined in a random subgroup of 58 patients. Analyses were performed immediately before the first donation and on the day prior to operation. Granulocytes increased during PABD by 4·6% (P < 0·01). Lymphocytes decreased by 8·8% (P < 0·01), accompanied by a relative rise in CD4+ T cells by 10·7% (P < 0·01) and in B cells by 10·3% (P < 0·01), and a fall of NK cells by 20·8% (P < 0·01). Stimulated TNF secretion of monocytes was suppressed (−12·3%, P < 0·01). The effect on the reactivity of lymphocytes and the T helper 1 (Th1)/Th2 balance were variable. The observed changes of innate and cellular immunity might influence the risk of perioperative infectious complications.