Optimal immunological homoeostasis determines the long-term recovery of patients in the postoperative period. The functional adaptability of monocytes plays a pivotal role in adjusting the host's response to an insult, immunostasis and long-term health, and may help to determine successful recovery. We undertook a longitudinal analysis of the functional adaptability of monocytes in 20 patients undergoing heart surgery with cardiopulmonary bypass, as a model of severe stress. Using each patient's pre-cardiopulmonary bypass data as a baseline, we investigated the characteristics of peripheral blood monocytes' functional plasticity in-vitro before elective bypass, and three months afterwards. Approximately 30% of subjects showed diminished monocyte plasticity, as demonstrated by decreased monocyte differentiation into dendritic cells three months after bypass. Diminished monocyte functional plasticity was related to over-production of macrophage colony-stimulating factor. Adding a neutralising antibody to macrophage colony-stimulating factor corrected the monocytes' differentiation defect. Finally, patients with reduced monocyte plasticity had significantly elevated serum C-reactive protein, with a concomitant increase in cytomegalovirus IgG antibody titres, suggestive of the acquisition of immuno-suppressive traits. Our study shows that severe surgical stress resulted in a lasting immunological defect in individuals who had seemingly recovered.